bims-mikwok Biomed News
on Mitochondrial quality control
Issue of 2026–07–26
fifty-six papers selected by
Gavin McStay, Liverpool John Moores University
  1. The role of exercise in MFN2 regulation in osteoarthritis.
  2. Disrupted Mitochondrial Quality Control in Atherosclerotic Disease: Mitophagy and Dynamics in Focus.
  3. Molecular Mechanisms Underlying FCCP-Induced Mitophagyin Human Airway Smooth Muscle Cells.
  4. FSH inhibits mitophagy via the mTOR/TFEB axis to preserve mitochondrial function in goat Sertoli cells.
  5. Chlamydia trachomatis Plasmid-Encoded Protein pORF5 Induces Mitochondrial Fission by Activating Drp1 via the MAPK/ERK Signaling Pathway.
  6. Microbiota-derived Indole-3-propionic acid improves FFA-induced liver injury in an in vitro model of nonalcoholic fatty liver disease by activating PINK1/parkin-mediated mitophagy.
  7. Methyltransferase METTL1 Upregulates USF2 in a m7G-Dependent Manner to Accelerate Septic Cardiomyopathy by Inactivating PINK1/Parkin-Mediated Mitophagy.
  8. [Effect of Huayu Tongluo moxibustion combined with neural stem cell transplantation on hippocampal Drp1/Mfn proteins and mitochondrial dynamics in rats with vascular dementia].
  9. Mitophagy suggesting a possible association with oocyte maturation: A study of granulosa cells from follicular fluid of normoresponder and diminished ovarian reserve cases.
  10. Metformin Ameliorates Diabetes-Associated Cognitive Dysfunction via p53/Parkin-Mediated Mitophagy.
  11. Activation of Mitophagy by Lidocaine Limits mROS and Prevents Microglial M1 Polarization to Alleviate Postoperative Delirium.
  12. PCSK9 inhibition alleviates sepsis-induced myocardial dysfunction by facilitating PINK1/parkin-associated mitophagy.
  13. SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response.
  14. 17β-Estradiol Maintains Mitochondrial Homeostasis in Osteoblasts by Inhibiting MMP-8 and Activating the Ras Signaling Pathway in Postmenopausal Osteoporosis.
  15. Mitochondrial transfer: quality dictates immune-metabolic fate.
  16. Corrigendum to "Selenium nanoparticles alleviate ulcerative colitis by regulating macrophage mitochondrial dynamics" [Free Rad. Biol. Med. 254 (2026) 323-341].
  17. HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway.
  18. Temporin-GHaR6R Peptide Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing Microglial M1 Polarization and Mitochondrial Dynamics Dysfunction.
  19. Qi Huang granules attenuate sodium iodate-induced retinal injury and inflammation via regulation of mitochondrial dynamics homeostasis.
  20. Systems pharmacology and targeted transcriptional profiling suggest the putative neuroprotective role of Leuconostoc mesenteroides in an in vitro Alzheimer's disease model.
  21. Electroacupuncture mitigates cognitive impairment caused by CPB by facilitating PINK1-dependent mitophagy and synaptic plasticity.
  22. Dual-regulation of mitophagy and cytosolic mtDNA-induced inflammation for the treatment of inflammatory bone loss.
  23. Mitochondrial dynamics and antiviral responses in Atlantic salmon cardiomyocytes during piscine myocarditis virus infection.
  24. Mailuo Shutong pills alleviate limb swelling in femoral fracture rats by orchestrating mitophagic clearance and ferroptotic suppression.
  25. Salidroside ameliorated high-altitude exposure induced retinal ganglion cell death by activating HIF-1α/BNIP3 signaling mediated mitophagy and inhibiting ferroptosis.
  26. Retraction notice to "Molecular structure and protein function of mitochondrial fusion protein Mfn2 alleviate Alzheimer's disease: exercise assisted regulation" [Int. J. Biol. Macromol. 311 (2025) 143696].
  27. Miro1-mediated mitochondrial transfer boosts stem cell therapy for muscle atrophy via restoring mitochondrial homeostasis.
  28. Impaired mitochondrial quality control and stress signalling machinery modulate senescence induction by genotoxic challenge.
  29. Artificial Chlorella Biohybrids for Alleviation of Cartilage Degeneration in Osteoarthritis.
  30. DRP1 lysine 616 lactylation exacerbates cerebral ischemia-reperfusion injury by activating the STING inflammatory pathway.
  31. Trimethylamine N-oxide activates cardiac fibroblasts transformation through NLRP3 inflammasome activation with changes in mitochondrial dynamics and ER-mitochondrial contact under ER stress.
  32. Nanozyme-integrated hydrogel orchestrates mitochondrial quality control to counter inflammatory and oxidative milieu during disc degeneration.
  33. SelO-mediated NAD+ hydrolysis safeguards mitochondrial homeostasis.
  34. M2 macrophage-derived exosomes improves secondary lymphedema through cellular mitochondrial homeostasis regulation via the Keap1-Nrf2/mPTP axis.
  35. CX3CR1+ macrophages aggravate doxorubicin-induced cardiomyopathy by impairing cardiac mitophagy via the CSF1R-PARP1-IL1B axis.
  36. VAMP7-dependent mitochondria-lysosome contacts contribute to glial mitochondrial dynamics and dopaminergic neuron survival.
  37. Fibroblast S1PR2 Amplifies NLRP3 Inflammasome Activation Under Pressure Overload.
  38. FGF20 relieves high glucose-induced Schwann cell mitochondrial damage through the activation of SIRT1.
  39. Tubular tRF‑1:30‑Gln‑CTG‑4 attenuates tubulointerstitial fibrosis by mitigating FBXO7-mediated mitophagy defect in diabetic kidney disease.
  40. HSP90α lactylation orchestrates PGC1α and LRPGC1 nuclear translocation driving mitochondrial biogenesis.
  41. Naotaifang Formula Suppresses Ferroptosis by Ameliorating Mitochondrial Biogenesis Through the Nrf2/TFAM Pathway in Ischemic Stroke.
  42. Screening of Biomarkers Related to Mitophagy in Severe Pancreatitis Based on Bioinformatics Methods.
  43. Calcium-dependent redox signaling connects mitochondrial remodeling with PAD-associated NETosis during respiratory mycoplasma infection.
  44. Mitochondrial reprogramming in cervical cancer: crosstalk with tumor immunity, HPV oncogenic signaling, and therapeutic resistance.
  45. Effects of 8-Week Exercise Snacks on Muscle Oxygenation and Cardiometabolic, Mitochondrial and Subclinical Atherosclerosis Markers in Sedentary Women.
  46. Mitochondria-targeted reactive species scavenger JP4-039 protects against disturbances of redox homeostasis, mitochondrial quality control, and glucose metabolism in brains of glutaryl-CoA dehydrogenase-deficient mice: A potential new therapeutic strategy for glutaric acidemia type 1.
  47. α-Ketoglutarate attenuates ammonium chloride-induced ferroptosis by maintaining mitochondrial homeostasis in grass carp (Ctenopharyngodon idellus) hepatocytes.
  48. The SIRT gene family protects against oxidative stress and mitochondrial dynamic dysfunction induced by polystyrene nanoplastics in the ovaries of zebrafish (Danio rerio).
  49. Bioinformatics, Machine Learning and Functional Validation Reveal Mitophagy-Related FABP5 and HMOX1 as Diagnostic and Therapeutic Targets in Polycystic Ovary Syndrome.
  50. Mitochondrial fission-mediated podocyte dysfunction via CaMKII/Drp1 signaling pathways contributes to lenvatinib-induced renal injury.
  51. Mitochondrial dysfunction and the regulatory cell death crosstalk network in chronic obstructive pulmonary disease: from oxidative stress mechanisms to targeted therapeutic strategies.
  52. Gut Microbial Release of Ferulic Acid From Germinated Quinoa Alleviates Obesity-Associated Cognitive Impairment by Activating Hippocampal Mitophagy Associated with PINK1/Parkin Pathway.
  53. Mitochondrial engineering strategies in yeast cell factories.
  54. A Blood-Derived Factor Rescues ALS: Platelet Factor 4 Activates OPTN-Dependent Autophagy to Clear SOD1 Aggregates Independently of PINK1.
  55. Retraction notice to "CircTMEM165 facilitates endothelial repair by modulating mitochondrial fission via miR-192/SCP2 in vitro and in vivo" [iScience 27 (2024) 109502].
  56. Mitochondria-targeted MXene-based nanozymes promote mitophagy and inhibit mtDNA-triggered cGAS/STING inflammation in osteoarthritis.
  1. Mol Biol Rep. 2026 Jul 18. pii: 1206. [Epub ahead of print]53(1):
    The role of exercise in MFN2 regulation in osteoarthritis.
    Jamal Alshorman, Ruba Altahla, Muhammad Umar.
      Osteoarthritis (OA) is currently the most prevalent degenerative joint disorder worldwide, with hallmarks including cartilage deterioration, low-grade inflammation, and mitochondrial dysfunction. In spite of intensive studies conducted in decades, there is still no disease-modifying treatment available. Mitofusin 2 (MFN2), one of the major mitochondrial fusion regulators, was recently identified as a pivotal molecular interface between mitochondria dynamics and chondrocyte differentiation in osteoarthritic joints. MFN2 demonstrates contradictory functions in the development of OA: protective in the physiological state and pathological when its function is deregulated. Safe, economic, and non-pharmacologic approach, exercise is capable of altering MFN2 expression via various mechanisms including AMPK/PGC-1α-mediated mitochondrial biogenesis, mitophagy due to mechanical loading, and anti-inflammatory NF-κB signaling. This review synthesizes current evidence, primarily from preclinical studies, suggesting that MFN2 may be a key molecular hub linking exercise to mitochondrial homeostasis in OA. We propose a testable model wherein exercise regulates MFN2 expression and function, potentially contributing to chondroprotection. However, we emphasize that the causal relationship remains to be established through targeted validation studies.
    Keywords:  AMPK; Autophagy; Exercise therapy; Ferroptosis; Mitochondrial dynamics; Mitofusin 2; Osteoarthritis; PGC-1α
    DOI:  https://doi.org/10.1007/s11033-026-12415-4
  2. JACC Basic Transl Sci. 2026 Jul 23. pii: S2452-302X(26)00144-0. [Epub ahead of print]11(8): 101625
    Disrupted Mitochondrial Quality Control in Atherosclerotic Disease: Mitophagy and Dynamics in Focus.
    Taylor Wilcox, Julie Hansen, Andrew Blanker, Michael E Widlansky.
      Mitochondrial health is essential for maintaining cardiac function, and mitophagy-the selective degradation of damaged mitochondria-is central to maintenance of mitochondrial quality. In this review, we focus on the role of mitophagy in atherosclerotic disease, exploring both canonical and noncanonical pathways. We aim to highlight how proper regulation of mitophagy supports cardiac health, while imbalances in this process can contribute to the onset and progression of cardiovascular conditions. In addition, we examine the cardioprotective potential of mitophagy in the context of disease and discuss its close relationship with mitochondrial dynamics, particularly as they relate to both macrovascular and microvascular dysfunction. Finally, we identify current gaps in knowledge and outline key questions that remain for the field to address, with the goal of guiding future research in this critical area of cardiovascular biology.
    Keywords:  atherosclerotic disease; mitochondrial dynamics; mitophagy
    DOI:  https://doi.org/10.1016/j.jacbts.2026.101625
  3. Am J Physiol Lung Cell Mol Physiol. 2026 Jul 23.
    Molecular Mechanisms Underlying FCCP-Induced Mitophagyin Human Airway Smooth Muscle Cells.
    Sanjana Mahadev Bhat, Oscar A Ramirez Ramirez, Gary C Sieck.
      Mitophagy is a selective autophagic process that eliminates damaged mitochondria, which is essential for mitochondrial quality control and cellular homeostasis. The most extensively characterized mitophagy pathway involves PTEN-induced kinase 1 (PINK1) and E3 ubiquitin ligase Parkin. Upon mitochondrial depolarization, PINK1 stabilizes on the outer mitochondrial membrane (OMM), where it recruits and phosphorylates Parkin at serine 65 (pParkinS65), activating its E3 ligase activity. Active pParkinS65 initiates the ubiquitination (Ub) of OMM proteins resulting in the engulfment and lysosomal degradation of damaged (depolarized) mitochondria. Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a mitochondrial uncoupler, is widely used to experimentally induce mitochondrial depolarization and initiate PINK1-Parkin-dependent mitophagy; however, mitophagic responses to FCCP vary across cell types. In the present study, we hypothesized that, in human airway smooth muscle (hASM) cells, FCCP-induced mitochondrial depolarization activates the PINK1-Parkin-mediated mitophagy pathway, culminating in the clearance of damaged mitochondria. We observed that exposing hASM cells to 1 µM FCCP for 6 h induced mitochondrial depolarization and a decrease in the volume of intact mitochondria. This mitochondrial depolarization triggered the accumulation of PINK1 in the mitochondria, which mediated phosphorylation of pParkinS65 and an increase in pUbS65 proteins. Confocal imaging of labeled mitochondria and lysosomes demonstrated increased colocalization of mitochondria with lysosomes, and mitophagic flux was confirmed using a pH-sensitive mitochondrial reporter mKeima. Collectively, these findings demonstrate that FCCP robustly activates the canonical PINK1-Parkin mitophagy pathway in hASM cells, providing mechanistic insight into mitochondrial quality control, with potential relevance to airway diseases characterized by mitochondrial dysfunction and altered hASM function.
    Keywords:  FCCP; Mitochondrial Quality Control; Mitophagy; PINK1; Parkin
    DOI:  https://doi.org/10.1152/ajplung.00050.2026
  4. Theriogenology. 2026 Jul 21. pii: S0093-691X(26)00278-5. [Epub ahead of print]265 118088
    FSH inhibits mitophagy via the mTOR/TFEB axis to preserve mitochondrial function in goat Sertoli cells.
    Huaming Xi, Feng Jiang, Xianglong Wang, Juan Li, Dong Niu.
      Sertoli cells sustain spermatogenesis by providing metabolic and structural support to germ cells. However, how endocrine signals regulate mitochondrial quality control, particularly mitophagy, in Sertoli cells remains unclear. Here, we investigated the role of follicle-stimulating hormone (FSH) in modulating mitophagy and mitochondrial function in primary goat Sertoli cells. FSH treatment increased the expression of LC3-II, PINK1 and Parkin, indicating activation of mitophagy initiation. However, the accumulation of p62 and the reduced colocalization between mitochondria and lysosomes revealed that FSH inhibited mitophagic flux by impairing autophagic degradation. FSH suppressed the nuclear translocation of transcription factor EB (TFEB) through activation of the mTOR pathway, thereby reducing lysosomal biogenesis and autophagic degradation capacity. Pharmacological and genetic manipulation of TFEB confirmed that TFEB is required for maintaining mitophagy and lysosomal function in Sertoli cells. Inhibition of mitophagy preserved mitochondrial integrity. Moreover, FSH-mediated suppression of mitophagy enhanced Sertoli cell metabolic and secretory activities, including lactate production and the secretion of key regulatory factors. Conditioned medium from FSH-treated Sertoli cells significantly promoted spermatogonial stem cell (SSC) proliferation and differentiation, indicating that Sertoli cell mitophagy indirectly regulates SSC fate. Collectively, our findings reveal that FSH restrains mitophagic flux via the mTOR/TFEB axis, thereby preserving mitochondrial function and enhancing Sertoli cell support capacity for SSC development. These findings identify FSH as a key regulator of mitophagy that preserves mitochondrial function and enhances the supportive capacity of Sertoli cells for SSC development.
    Keywords:  Follicle-stimulating hormone; Mitophagy; Sertoli cells; Spermatogenesis; Transcription factor EB
    DOI:  https://doi.org/10.1016/j.theriogenology.2026.118088
  5. Microbiol Immunol. 2026 Jul 22.
    Chlamydia trachomatis Plasmid-Encoded Protein pORF5 Induces Mitochondrial Fission by Activating Drp1 via the MAPK/ERK Signaling Pathway.
    Yan Zou, Silu Gong, Liuliang Guo, Boru Tang, Jun Zhang.
      Chlamydia trachomatis (C. trachomatis) is a strictly parasitic pathogen that heavily relies on host cells for generating energy, acquiring nutrients, and evading immune responses. Mitochondrial dynamics-the balance of fusion and fission-are integral to cellular functions, including the maintenance of homeostasis, the regulation of metabolic processes, and the modulation of host innate immune pathways. Accordingly, C. trachomatis can specifically change the host mitochondrial dynamics to promote its intracellular replication. Mitochondrial fragmentation has been observed during the later phases of C. trachomatis infection; Nevertheless, the exact mechanisms remain poorly defined. The research aimed to determine the effect of the C. trachomatis secretory protein pORF5 in this process. In stable pORF5-expressing Hela cells, we employed confocal microscopy to analyze mitochondrial morphology and Western blotting to measure the expression of key mitochondrial dynamics proteins. Finally, immunofluorescence was used to monitor Drp1 mitochondrial translocation, and the effects of a pathway inhibitor on mitochondrial fission were evaluated. We observed that the plasmid-encoded protein pORF5 can induce mitochondrial fission. Mechanistically, this process is dependent on the activation of the ERK/Drp1 signaling axis, which indicates the crucial importance of this pathway and its effect on pORF5-induced mitochondrial fragmentation.
    Keywords:  Chlamydia trachomatis; Drp1; MAPK/ERK signal pathway; mitochondrial fission; pORF5
    DOI:  https://doi.org/10.1111/1348-0421.70082
  6. Toxicol In Vitro. 2026 Jul 22. pii: S0887-2333(26)00087-1. [Epub ahead of print] 106279
    Microbiota-derived Indole-3-propionic acid improves FFA-induced liver injury in an in vitro model of nonalcoholic fatty liver disease by activating PINK1/parkin-mediated mitophagy.
    Qilin Liu, Dahai Wu, Linhua Teng, Gengyang Lin, Huali Hua, Zhihai Liang.
       BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern, and its pathology is associated with impaired hepatic mitochondrial function and disrupted mitophagy. Emerging evidence highlights gut microbiota-derived metabolites as key regulators of NAFLD progression. Indole-3-propionic acid (IPA), a microbiota-derived tryptophan metabolite, has been linked to NAFLD development. However, its influence on mitophagy remains poorly defined.
    METHODS: In vitro, HepG2 cells were treated with free fatty acid (FFA) to establish a NAFLD model, followed by IPA treatment. The mRNA and protein expression levels were analyzed by qRT-PCR, Western blot, and immunofluorescence staining. Cell viability, oxidative stress, apoptosis, and mitochondrial function were assessed via CCK-8, ELISA, flow cytometry, and JC-1 staining. PINK1-USP4 interaction and ubiquitination were examined using co-IP and ubiquitination assays.
    RESULTS: Serum IPA levels were significantly reduced in NAFLD patients. In FFA-treated HepG2 cells, IPA attenuated oxidative injury while restoring mitochondrial function. Mechanistically, IPA activated PINK1/Parkin-mediated mitophagy by upregulating USP4, which stabilized PINK1 via deubiquitination. PINK1 or USP4 knockdown abolished IPA's protective effects against FFA-induced oxidative injury and mitophagy impairment in hepatocytes.
    CONCLUSION: IPA alleviated FFA-induced oxidative injury in hepatocytes by activating PINK1/Parkin-mediated mitophagy via USP4-dependent PINK1 deubiquitination. These findings reveal a gut microbiota-mitochondria axis in NAFLD and suggest IPA as a potential therapeutic strategy targeting the USP4-PINK1 pathway.
    Keywords:  Indole-3-propionic acid; Mitophagy; Non-alcoholic fatty liver disease; PINK1/Parkin pathway; USP4
    DOI:  https://doi.org/10.1016/j.tiv.2026.106279
  7. Cardiovasc Toxicol. 2026 Jul 23. pii: 84. [Epub ahead of print]26(8):
    Methyltransferase METTL1 Upregulates USF2 in a m7G-Dependent Manner to Accelerate Septic Cardiomyopathy by Inactivating PINK1/Parkin-Mediated Mitophagy.
    Wei Dong, Jin Chen, Zhiping Xiong, Ruichun Liao, Junfei Weng, Zhichao Wang, Xiaoping Peng.
      Septic cardiomyopathy (SCM) is a severe complication of sepsis, characterized by high mortality. The activation of mitophagy in cardiomyocytes is crucial for alleviating SCM. The N7-methylguanosine (m7G) modification mediated by methyltransferase 1 (METTL1) is known to negatively regulate mitophagy. This study investigated the mechanism of METTL1 in the mitophagy of cardiomyocytes in SCM. Human cardiomyocytes (HCMs) were stimulated with lipopolysaccharide (LPS) to establish the SCM model. C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to create a septic model. Mitophagy was assessed utilizing the mt-Keima assay, while mitochondrial membrane potential was measured with the JC-1 assay. MitoSOX Red assay was employed to evaluate levels of mitochondrial reactive oxygen species (ROS). The interaction between METTL1 and upstream transcription factor 2 (USF2), as well as between USF2 and PTEN-induced putative kinase protein 1 (PINK1), was confirmed through RNA immunoprecipitation (RIP) and RNA pull-down or dual luciferase reporter gene and chromatin immunoprecipitation (ChIP) assays. The silenced METTL1 mitigated LPS-triggered myocardial damage in vitro. The inhibition of mitophagy nullified the protective effects conferred by METTL1 silencing in LPS-induced HCMs. Consistently, METTL1 silencing ameliorated myocardial injury induced by sepsis in a mouse model. METTL1 enhanced the expression of USF2 in an m7G-dependent manner. USF2, in turn, inactivated the PINK1/Parkin signaling pathway by repressing PINK1 transcription. The repression of USF2 negated the protective effects of METTL1 silencing on myocardial damage and mitophagy. METTL1 aggravated myocardial injury by inhibiting PINK1/Parkin-mediated mitophagy through the upregulation of USF2 in a m7G-dependent manner in SCM models, thereby identifying METTL1 as a potential therapeutic target for SCM.
    Keywords:  METTL1; Mitophagy; PINK1/Parkin; SCM; USF2
    DOI:  https://doi.org/10.1007/s12012-026-10144-5
  8. Nan Fang Yi Ke Da Xue Xue Bao. 2026 Jul 20. pii: 1673-4254(2026)07-1520-13. [Epub ahead of print]46(7): 1520-1532
    [Effect of Huayu Tongluo moxibustion combined with neural stem cell transplantation on hippocampal Drp1/Mfn proteins and mitochondrial dynamics in rats with vascular dementia].
    Weishuai Yin, Fei Li, Yi Cao, Qiqi Yang, Zetian Deng, Shijie Cao, Yongqi Sun, Xinyang Bi, Zhengpeng Liang, Sijia Wu, Baoguo Wang.
       OBJECTIVES: To investigate the mechanism by which Huayu Tongluo moxibustion (HYTLM) regulates mitochondrial dynamics of neural stem cells (NSCs) for treatment of vascular dementia (VD).
    METHODS: Seventy-two SD rats were randomized equally into 6 groups, including a sham-operated group, a VD model group, and 4 VD groups receiving HYTLM treatment, HYTLM treatment with stereotactic injection of NSC suspension into the hippocampal CA1 region, or injections of NSC suspension or cell culture medium without HYTLM treatment. Morris water maze test was used to assess learning and memory ability of the rats. Hippocampal neuronal apoptosis, NSC differentiation, neuronal survival, histopathological changes, mitochondrial reactive oxygen species (ROS) levels, and hippocampal expressions of Drp1, Mfn1, Mfn2, and Fis1 proteins were evaluated using TUNEL assay, immunofluorescence staining, HE staining, flow cytometry, and Western blotting.
    RESULTS: The rats receiving culture medium injection, similar to the VD rats, exhibited prolonged escape latency and disorganized swimming trajectories in Morris water maze test and had significantly increased neuronal apoptosis, suppressed NSC proliferation, reduced mature neurons, impaired neurogenesis, and increased ROS levels in the hippocampal CA1 region, showing also obvious neuronal injuries, lowered hippocampal Drp1, Mfn1, and Mfn2 expressions and increased Fis1 expression. All these changes were significantly alleviated in VD rats receiving NSC transplantation. HYTLM treatment produced similar effects to NSC transplantation, but their combined treatment further shortened the escape latency of the VD rats, which showed similar swimming patterns to the sham-operated rats, and produced stronger protective effects on the hippocampal neurons. The combined treatment also further reduced ROS levels and improved aberrant expressions of Drp1, Mfn1, Mfn2, and Fis1.
    CONCLUSIONS: HYTLM treatment improves cognitive functions of VD rats, promotes NSC differentiation into functional neurons and neuronal survival, and attenuates neuronal injury possibly by regulating hippocampal mitochondrial dynamics, thereby restoring mitochondrial homeostasis and ameliorating functional impairment.
    Keywords:  Huayu Tongluo moxibustion; mitochondrial dynamics; neural stem cells; neurons; vascular dementia
    DOI:  https://doi.org/10.12122/j.issn.1673-4254.2026.07.06
  9. Sci Prog. 2026 Jul-Sep;109(3):109(3): 368504261466808
    Mitophagy suggesting a possible association with oocyte maturation: A study of granulosa cells from follicular fluid of normoresponder and diminished ovarian reserve cases.
    Çağrı Öner, Damla Kolcuoğlu, Nergis Özlem Kiliç, Defne Dumanli, Ahmet Can Çelik, Alara Kaya, Baturalp Bakirci, Sena Köstü, Ece Bilge Şimşek, Belgin Selam, Ertuğrul Çolak.
      ObjectiveThis study investigated mitophagy, a kind of mitochondrial dysfunction, as a biomarker for oocyte maturation by analyzing granulosa cells from follicular fluid in normoresponder (NOR) and diminished ovarian reserve (DOR) cases. The aim was to evaluate the expression of mitochondrial dynamics genes, Mitofusin-1 (MFN-1), Mitofusin-2 (MFN-2), and PARKIN, in granulosa cells surrounding oocytes at Metaphase I (MI) and Metaphase II (MII) stages.MethodsIn this experimental study, follicular fluid samples were collected from 30 NOR and 30 DOR women undergoing IVF and subdivided according to MI and MII oocyte maturation stages. Granulosa cells were isolated, morphologically assessed, and analyzed for gene expression using qRT-PCR.ResultsNOR MII granulosa cells exhibited the healthiest morphology and highest cell numbers, while DOR MI samples showed the most degeneration. MFN-1 expression was significantly decreased in DOR MI compared to NOR MI, while MFN-2 was higher in DOR MI and NOR MII. PARKIN expression was lower in DOR compared to NOR in both MI and MII. Correlation analysis revealed strong positive relationships among MFN-1, MFN-2, and PARKIN in NOR MII.ConclusionsThese findings suggest that mitophagy-related gene expression profiles in granulosa cells may serve as non-invasive biomarkers for predicting oocyte quality and embryo development in IVF.
    Keywords:  MFN-1; MFN-2; PARKIN; diminished ovarian reserve; follicular fluid; normoresponder
    DOI:  https://doi.org/10.1177/00368504261466808
  10. Diabetes Obes Metab. 2026 Jul 19.
    Metformin Ameliorates Diabetes-Associated Cognitive Dysfunction via p53/Parkin-Mediated Mitophagy.
    Wangjun Xu, Lulu Di, Xian Wang, Qinghe Miao, Jingwei Sun, Ran Zhao, Xinmei Xie, Yangyang He, Xi Li, Yunfeng Zhou, Lida Du, Xiaobin Pang.
       BACKGROUND: Diabetes-associated cognitive dysfunction (DACD) is a common and serious diabetic complication, and emerging evidence has identified impaired mitophagy as its potential pathological feature. Metformin (Met) possesses both hypoglycemic and cognitive-enhancing activities, and also exerts modulatory effects on mitophagy. However, the precise mechanisms by which it regulates mitophagy to ameliorate DACD remain poorly understood.
    AIMS: Our present study aims to verify the ameliorative effects of Met on cognitive dysfunction in DACD mice, and to explore its underlying mechanisms.
    MATERIALS AND METHODS: Cognitive function of type 2 diabetes mellitus (T2DM) mice was evaluated by behavioural tests after Met administration. Proteomic profiling and multiple molecular biology techniques were utilised to explore and validate the effect of Met on mitophagy in T2DM mice, as well as in high glucose (HG)-injured HT22 and SH-SY5Y cells.
    RESULTS: We found that Met significantly alleviated cognitive impairment and neuronal damage in T2DM mice. Proteomic analysis indicated that the effect of Met in improving cognition might be closely related to mitophagy regulation. Furthermore, Met markedly downregulated Beclin1, Atg4, Atg7, LC3 II, PINK1, and Parkin in the hippocampus of T2DM mice, while upregulating p62 levels. Simultaneously, Met reduced the colocalisation of mitochondria and autophagosome marker LC3B, and the colocalisation of mitochondria and lysosome. These results indicated that Met could reverse excessive mitophagy activation. Moreover, Met dramatically increased the cytoplasmic expression of p53 and Parkin, while inhibiting the translocation of Parkin to damaged mitochondria. Consistent results were also observed in HG-injured HT22 and SH-SY5Y cells after Met incubation. Notably, the effect of Met on mitophagy and p53 was blocked by the p53 inhibitor PFT-α.
    DISCUSSION: Our study confirmed that Met inhibited the mitochondrial localisation of Parkin by elevating cytosolic p53 levels, thereby preventing excessive mitophagy and ameliorating DACD.
    CONCLUSION: These findings indicated that Met might have potential for clinical repurposing in the treatment of DACD.
    Keywords:  diabetes‐associated cognitive dysfunction; metformin; mitophagy; p53/Parkin pathway
    DOI:  https://doi.org/10.1111/dom.71093
  11. Behav Brain Res. 2026 Jul 24. pii: S0166-4328(26)00374-8. [Epub ahead of print] 116398
    Activation of Mitophagy by Lidocaine Limits mROS and Prevents Microglial M1 Polarization to Alleviate Postoperative Delirium.
    Qingfu Wang, Qiang Du, Xilin Chen, Lifeng Ni, Wenying Lu, Shengjie Yao, Jing Yu, Congzhong Song, Dongqiang Wang, Shaobao Song.
       OBJECTIVE: Postoperative delirium (POD) is a common complication in elderly patients, yet effective interventions remain limited. Mitochondrial dysfunction and microglial M1 polarization contribute to POD pathogenesis, but the underlying mechanisms are incompletely understood. This study aimed to investigate whether lidocaine (LID) ameliorates POD by activating mitophagy to suppress mitochondrial reactive oxygen species (mROS) and inhibit M1 microglial polarization.
    METHODS: A mouse model of POD was established by laparotomy in male C57BL/6J mice, which were randomly divided into four groups (n=6 each): sham, POD, POD+LID (8mg/kg, i.v.), and POD+LID+Mdivi‑1 (25mg/kg, i.p.). Behavioral tests (open field and Y‑maze), serum inflammatory and oxidative markers, hippocampal histology, mitophagy-related proteins, microglial polarization markers, mROS, and ATP were assessed. In vitro, LPS-stimulated BV2 cells were treated with LID (10μg/mL), Mdivi‑1 (5μM), or the mROS scavenger Mito‑TEMPO (1.5mM) to evaluate mitochondrial function, mROS, and polarization.
    RESULTS: LID treatment significantly improved behavioral performance, as evidenced by increased central zone exploration and Y‑maze alternation rate, reduced serum TNF‑α and IL‑1β, elevated IL‑10, and attenuated oxidative stress (decreased MDA, increased SOD) in POD mice. LID also restored hippocampal mitochondrial morphology, enhanced mitophagy (reduced p62, increased PINK1, Parkin, and LC3‑II/LC3‑I ratio), and shifted microglial polarization from M1 (decreased CD86/iNOS) to M2 (increased CD206/Arg‑1). All these effects were reversed by Mdivi‑1. In BV2 cells, LID reduced pro‑inflammatory cytokines (TNF‑α, IL‑1β), increased IL‑10, restored mitochondrial membrane potential, decreased mROS, and promoted M2 polarization; these effects were blocked by Mdivi‑1 and rescued by Mito‑TEMPO.
    CONCLUSION: LID activates mitophagy, reduces mROS, and promotes M2 microglial polarization, thereby alleviating POD, highlighting its therapeutic potential.
    Keywords:  Lidocaine; Microglial polarization; Mitophagy; Neuroinflammation; Postoperative delirium
    DOI:  https://doi.org/10.1016/j.bbr.2026.116398
  12. Front Pharmacol. 2026 ;17 1844269
    PCSK9 inhibition alleviates sepsis-induced myocardial dysfunction by facilitating PINK1/parkin-associated mitophagy.
    Jiancheng Lin, Zetao Pan, Jiayan Sun, Xiaowan Wang, Linna Zhang, Yuheng Ye, Di Yin, Yi Wang, Qiang Guo.
       Introduction: Sepsis-induced myocardial dysfunction (SIMD), also known as septic cardiomyopathy in sepsis patients is associated with worse prognosis and higher mortality compared to sepsis cases without SIMD. Early intervention and comprehensive management are crucial for improving survival, particularly in the early stages of sepsis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising therapeutic target in the cardiovascular system. While PCSK9 has been implicated in cardiovascular inflammation and injury, specific evidence regarding the potential of PCSK9 inhibition to mitigate SIMD remains limited.
    Methods: An in vivo mouse model of sepsis was established using cecal ligation and puncture (CLP), and SIMD was assessed through echocardiography and right ventricular systolic pressure measurements. For in vitro cellular SIMD models, lipopolysaccharide was administered to HL-1 and H9c2 cardiomyocytes. Data concerning apoptosis, inflammatory responses, oxidative stress, and mitophagy were evaluated across both models.
    Results: The SIMD models were successfully established both in vivo and in vitro. PCSK9 inhibition visibly attenuated myocardial dysfunction, cellular injury, apoptosis, inflammation, and oxidative stress, which was accompanied by enhanced mitophagic clearance. Furthermore, the application of Mdivi-1, a mitochondrial division inhibitor that impairs mitophagy, revealed that the cardioprotective effects of PCSK9 inhibition are at least partially dependent on the preservation of mitophagy. Mechanistically, PCSK9 inhibition appeared to facilitate mitophagic flux in SIMD, potentially via the PINK1/Parkin signaling pathway.
    Conclusion: These findings suggest that the protective effects of PCSK9 inhibition against SIMD are closely associated with the enhancement of mitophagy and the modulation of the PINK1/Parkin pathway. Furthermore, this intervention correlates with attenuated oxidative stress, inflammation, and apoptosis, ultimately offering a potential therapeutic strategy for myocardial injury.
    Keywords:  PCSK9; evolocumab; mitochondrial dynamics; mitochondrial quality control; mitophagy; sepsis-induced myocardial dysfunction
    DOI:  https://doi.org/10.3389/fphar.2026.1844269
  13. Cardiovasc Toxicol. 2026 Jul 23. pii: 86. [Epub ahead of print]26(8):
    SIRT5 Attenuates Doxorubicin-Induced Acute Cardiac Injury by Modulating PHB2 Succinylation and the Mitophagic Response.
    Aihui Zeng, Haiqiong Liu, Xudong Song, Jing Yan, Yan Zhou, Datong Sun, Aihua Chen.
      Doxorubicin (DOX)-induced cardiac injury remains a major limitation of chemotherapy and is closely linked to mitochondrial dysfunction, oxidative stress, and dysregulated mitophagy. Sirtuin 5 (SIRT5), a mitochondrial deacylation-related protein, has been implicated in mitochondrial homeostasis; however, its role in DOX-induced acute cardiaotoxicity is not fully understood. Here, we investigated whether SIRT5 mitigates acute DOX-induced cardiac injury by regulating prohibitin 2 (PHB2) succinylation and mitochondrial quality control. An acute DOX-induced cardiac-damaged mouse model was established (15 mg/kg for one single dose, i.p.) in male C57BL/6 mice, serum lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and cardiac creatine kinase isoenzyme MB (CK-MB) were elevated, accompanied by reduced cardiac SIRT5 expression. In primary cardiomyocytes, DOX (4 µM, 24 h) downregulated SIRT5 and induced excessive ROS production and apoptosis together with altered mitophagy-related signaling. SIRT5 overexpression attenuated DOX-triggered ROS accumulation and apoptosis and reversed these mitophagy-associated alterations. Mechanistically, PHB2 succinylation was increased upon DOX exposure, whereas SIRT5 overexpression reduced PHB2 succinylation detected by PHB2 immunoprecipitation followed by pan-succinyl-lysine immunoblotting. In addition, SIRT5 showed colocalization and interaction with PHB2. Collectively, our findings suggest that SIRT5 attenuates acute DOX-induced cardiotoxicity, potentially through modulating PHB2 succinylation and the mitophagic response, highlighting the SIRT5-PHB2 axis as a candidate target for alleviating early-onset of DOX-induced cardiac injury.
    Keywords:  Acute cardiac injury; Doxorubicin; Mitophagy; PHB2; SIRT5
    DOI:  https://doi.org/10.1007/s12012-026-10165-0
  14. FASEB J. 2026 Jul 31. 40(14): e72139
    17β-Estradiol Maintains Mitochondrial Homeostasis in Osteoblasts by Inhibiting MMP-8 and Activating the Ras Signaling Pathway in Postmenopausal Osteoporosis.
    Huan Min, Yuxu Li, Gang Chen, Jiabin Wen, Xi Li, Zhisheng Long, Jinhui Cheng.
      17β-estradiol is a potent endogenous estrogen used for postmenopausal osteoporosis treatment. Its osteoprotective role correlates with matrix metalloproteinase (MMP) and mitochondrial homeostasis. This research sought to examine the role of 17β-estradiol on MMP-8 in mitochondrial homeostasis and elucidate the potential regulatory pathways. We evaluated the effects of 17β-estradiol on MMP-8, bone loss, osteogenic differentiation, and mitochondrial homeostasis in bilateral ovariectomy (OVX)-induced mice and MC3T3-E1 cells. MMP-8 was overexpressed to validate its regulatory relationship with 17β-estradiol. Comprehensive analyses were further conducted to identify the potential pathways associated with MMP-8. The Ras pathway agonist ML-099 and inhibitor Lonafarnib were used for pathway validation. 17β-estradiol treatment attenuated bone loss and increased osteogenic Ca2+, osteoprotegerin (OPG), and osteocalcin (OC) levels. It inhibited reactive oxygen species (ROS) and malondialdehyde (MDA), promoted superoxide dismutase (SOD) activity, and restored mitochondrial homeostasis via upregulating the expression of dynamin-related protein 1 (DRP1), mitofusin 1 (MFN1), and peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α), accompanied by increased adenosine triphosphate (ATP), mitochondrial membrane potential, and mitochondrial oxygen consumption. MMP-8 overexpression significantly reversed these protective effects. The Ras pathway was identified as a potential pathway associated with MMP-8-mediated osteoporosis regulation. ML-099 administration in 17β-estradiol + MMP-8 overexpression cells markedly restored mitochondrial homeostasis and rescued osteogenic differentiation. Conversely, the adverse impacts of MMP-8 overexpression on osteoblast differentiation, mitochondrial homeostasis, and Ras activation were further aggravated by Lonafarnib treatment. 17β-estradiol maintains mitochondrial homeostasis in osteoblasts via inhibiting MMP-8 and activating the Ras pathway, which provides novel potential targets for postmenopausal osteoporosis management.
    Keywords:  17β‐estradiol; MMP‐8; Ras signaling pathway; mitochondrial homeostasis; osteoporosis
    DOI:  https://doi.org/10.1096/fj.202601404R
  15. Trends Mol Med. 2026 Jul 23. pii: S1471-4914(26)00172-3. [Epub ahead of print]
    Mitochondrial transfer: quality dictates immune-metabolic fate.
    Kai Liu, Quazi T H Shubhra, Hui Zhang.
      Horizontal mitochondrial transfer (HMT) outcomes are shaped by donor fitness and transfer context. We propose a post-transfer quality checkpoint that integrates membrane potential, oxidative damage, mitophagy, fusion, and fission to determine the recipient-cell's response. Depending on donor quality and recipient thresholds, HMT may drive bioenergetic restoration, inflammation, or tumor immune escape. This framework extends route-centered accounts of HMT toward a testable, quality-governed model for therapeutic intervention.
    Keywords:  immune-metabolic fate; mitochondrial quality; mitochondrial transfer; quality checkpoint
    DOI:  https://doi.org/10.1016/j.molmed.2026.07.002
  16. Free Radic Biol Med. 2026 Jul 24. pii: S0891-5849(26)00965-2. [Epub ahead of print]
    Corrigendum to "Selenium nanoparticles alleviate ulcerative colitis by regulating macrophage mitochondrial dynamics" [Free Rad. Biol. Med. 254 (2026) 323-341].
    Jiajing Chang, Xiaonan Zeng, Runan Zhang, Tiantian Li, Qianqian Gao, Chunlan Xu.
      
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.07.038
  17. Autophagy. 2026 Jul 22.
    HTLV-1 Tax induces PINK1-PRKN/parkin-dependent mitophagy to mitigate activation of the CGAS-STING1 pathway.
    Suchitra Mohanty, Sujit Suklabaidya, Nelli Mnatsakanyan, Steven Jacobson, Edward W Harhaj.
      Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax regulatory protein plays a critical role in HTLV-1 persistence and pathogenesis; however, the underlying mechanisms are poorly understood. Here we show that Tax dynamically regulates mitochondrial reactive oxygen species (ROS) and membrane potential to trigger mitochondrial dysfunction. Tax is recruited to damaged mitochondria through its interaction with the IKK regulatory subunit IKBKG/NEMO and directly engages the ubiquitin-dependent PINK1-PRKN/parkin pathway to induce mitophagy. Tax also recruits autophagy receptors CALCOCO2/NDP52 and SQSTM1/p62 to damaged mitochondria to induce mitophagy. Furthermore, Tax requires PRKN to limit the extent of CGAS-STING1 activation and suppress type I interferon (IFN) induction. HTLV-1-transformed T-cell lines and PBMCs from HAM/TSP patients exhibit hallmarks of chronic mitophagy, and inhibition of PRKN in HTLV-1-transformed cell lines downregulates p19 Gag expression and induces cell death. Collectively, our findings suggest that Tax manipulation of the PINK1-PRKN mitophagy pathway represents a new HTLV-1 immune evasion strategy important for maintaining viral gene expression and cell survival.
    Keywords:  CALCOCO2/NDP52; HTLV-1; IKBKG/NEMO; PINK1; PRKN/Parkin; STING1; mitochondria; mitophagy; reactive oxygen species; tax
    DOI:  https://doi.org/10.1080/15548627.2026.2707897
  18. Probiotics Antimicrob Proteins. 2026 Jul 21.
    Temporin-GHaR6R Peptide Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing Microglial M1 Polarization and Mitochondrial Dynamics Dysfunction.
    Da-Qi Zhang, Hui-Min Xu, Jing Lu, Yu-Sheng Huang, Xiao-Li Feng, Li-Jun Chen, Wen-Jie Zhao, Rong Wang, Yingxia Zhang, Qifu Li.
      Multiple sclerosis (MS), an immune-mediated inflammatory demyelinating disorder of the central nervous system (CNS), is driven by microglia as key orchestrators of neuroinflammation. This study assessed the preventive potential of temporin-GHaR6R (GHaR6R), an antimicrobial peptide derived from Hylarana guentheri skin, using the experimental autoimmune encephalomyelitis (EAE) murine model of MS. Preventive administration of GHaR6R significantly reduced EAE incidence and alleviated clinical severity, while histopathological analyses (HE and LFB staining) revealed attenuated inflammatory cell infiltration and demyelination in the spinal cord. Mechanistically, GHaR6R suppressed M1 microglial polarization, thereby limiting excessive neuroinflammatory activation. In vitro, GHaR6R inhibited TNF-α and IL-6 secretion, reduced mitochondrial ROS production, preserved mitochondrial membrane potential in LPS-activated BV2 microglia, and promoted the shift from M1 to M2 microglial polarization. Consistent with these findings, GHaR6R downregulated mitochondrial fission protein Drp-1 while upregulating the fusion mediators MFN1 and MFN2 in both EAE-affected spinal cords and LPS-stimulated BV2 cells. Immunofluorescence analysis showed increased colocalization of Iba-1 with MFN1/2, indicating enhanced mitochondrial fusion in microglia. Taken together, these results demonstrate that GHaR6R ameliorates EAE progression by modulating microglial mitochondrial dynamics, mitigating neuroinflammation, and inhibiting M1 polarization, highlighting its potential as an early prophylactic intervention for MS.
    Keywords:  EAE; GHaR6R; microglia; mitochondrial dynamics; mitochondrial fission and fusion
    DOI:  https://doi.org/10.1007/s12602-026-11143-2
  19. Int J Biochem Cell Biol. 2026 Jul 20. pii: S1357-2725(26)00104-4. [Epub ahead of print]200 107000
    Qi Huang granules attenuate sodium iodate-induced retinal injury and inflammation via regulation of mitochondrial dynamics homeostasis.
    Jifang Wang, Zhiqiang Wu, Lulu Fang, Yuxin Guo, Hongmei Li, Fengming Liang.
      Qi Huang Granules (QHG), a traditional Chinese medicine (TCM) formulation, have been applied clinically for over two decades to treat dry age-related macular degeneration (AMD) and associated fundus lesions. Although its retinoprotective effects have been documented, the associated underlying mechanisms are largely unexplored. The present work focused on investigating the therapeutic efficacy of QHG in sodium iodate (NaIO₃)-induced retinal damage, with a particular focus on how the formula regulated the interaction between inflammatory responses and imbalances in mitochondrial dynamics. UPLC-HRMS, network pharmacology, and molecular docking analyses were integrated for identifying mitochondria-associated bioactive constituents and potential targets of QHG. In the experimental model, retinal injury was induced in rats through tail vein injection of NaIO3. Retinal morphological and ultrastructural changes were assessed by HE staining and transmission electron microscopy. To assess mitochondrial function, mitochondrial membrane potential, mtROS levels, and mtDNA integrity were measured. Additionally, ELISA was performed to quantify IL-1β and IL-18 levels. Key marker levels, including p-DRP1, DRP1, OPA1, MFN2, and NLRP3, were determined by Western blotting, IHC, and qRT-PCR. DNM1L (encoding DRP1) and MFN2 were identified as the primary targets of QHG through UPLC-HRMS and computational analyses. In vivo experimental results showed that treatment with QHG alleviated morphological alterations and ultrastructural damage to the retina and mitochondria in model rats. Furthermore, QHG treatment increased mitochondrial membrane potential, reduced mtROS levels, mitigated mtDNA damage, and reduced IL-1β and IL-18 contents. Mechanistically, QHG downregulated p-DRP1, DRP1, and NLRP3, while upregulating MFN2 and OPA1. Collectively, these findings demonstrate that QHG can ameliorate retinal morphology and ultrastructural damage in mitochondria, such as cellular mitochondria, improve mitochondrial function, and attenuate retinal inflammation, thereby exerting a protective effect against NaIO₃-induced retinal injury. The underlying mechanism may involve the mitochondrial dynamics-NLRP3 pathway.
    Keywords:  Dry AMD; Inflammation; Mitochondrial Dynamics; NLRP3; Qihuang Granules (QHG)
    DOI:  https://doi.org/10.1016/j.biocel.2026.107000
  20. Mol Biol Rep. 2026 Jul 24. pii: 1255. [Epub ahead of print]53(1):
    Systems pharmacology and targeted transcriptional profiling suggest the putative neuroprotective role of Leuconostoc mesenteroides in an in vitro Alzheimer's disease model.
    Safaa Altves, Ebru Guclu, Esra Yetisgin, Kivanc Bilecen, Hasibe Vural.
       BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder driven by amyloid-beta (Aβ) accumulation, mitochondrial failure, and neuroinflammation. While probiotics show therapeutic potential via the gut brain axis, the molecular mechanisms remain poorly understood. This study investigated the neuroprotective potential of Leuconostoc mesenteroides lysate and its bioactive metabolites in an Aβ-induced SH-SY5Y neuroblastoma model.
    METHODS: SH-SY5Y cells were challenged with Aβ and treated with L. mesenteroides lysate. Neuroprotective effects were evaluated via ROS accumulation, SOD1, APOE, NOS2, and mitochondrial dynamics (MFF, OPA1) using qPCR and WB. Potential mechanisms of action were explored computationally through integrated genome mining (antiSMASH 7.0), molecular docking (CB-Dock2), and systems pharmacology analysis (STRING/KEGG/R-studio) to identify candidate metabolites and host targets.
    RESULTS: L. mesenteroides lysate significantly attenuated Aβ-induced ROS levels and upregulated SOD1, enhancing antioxidant capacity. The lysate effectively downregulated APOE expression and restored mitochondrial homeostasis by reducing mitochondrial fission (MFF) and promoting fusion (OPA1). In silico analysis predected phytoene as a primary bioactive metabolite with significant theoretical binding affinity for APOE. Systems biology mapping revealed highly significant enrichment in PPAR signaling and cholesterol metabolism pathways (FDR < 10⁻⁵). Specifically, Cellular Component analysis highlighted robust interactions within protein-lipid complexes (FDR = 1.98e-16).
    CONCLUSION: L. mesenteroides lysate counteracts Aβ-induced neurotoxicity by modulating oxidative stress and restoring mitochondrial bioenergetics. Collectively, our findings suggest a theoretical Phytoene-PPAR-APOE signaling axis as a predictive framework for the observed cellular effects. We emphasize that phytoene represents a predicted candidate metabolite requiring future chemical characterization and biological validation.
    Keywords:   Leuconostoc mesenteroides ; APOE; Alzheimer’s Disease; Mitochondrial Dynamics; PPAR Signaling; Phytoene
    DOI:  https://doi.org/10.1007/s11033-026-12446-x
  21. Behav Brain Res. 2026 Jul 22. pii: S0166-4328(26)00371-2. [Epub ahead of print] 116395
    Electroacupuncture mitigates cognitive impairment caused by CPB by facilitating PINK1-dependent mitophagy and synaptic plasticity.
    Chunxiao Liu, Yanying Zhang, Zhining Wang, Huisheng Huo, Jianli Cui, Yajing Zhang, Yanan Li, Lei Shi, Qi Zhang.
      Postoperative cognitive impairment has become the popular critical post-operative consequences, especially cardiopulmonary bypass(CPB), leading to an increased risk of mortality. However, there is no Effective treatment measures for CPB induced cognitive dysfunction. Electroacupuncture(EA) has shown promise in improving cognitive function, its efficacy in preventing cognitive impairment following CPB remains unknown. The current study aims to uncover the effect and mechanism of EA in relieving CPB induced cognitive dysfunction. The results showed that CPB notably impaired cognitive performance as well as restrained PINK1-mediated mitophagy, promoted reactive oxygen species (ROS) production and damaged synaptic function in the hippocampal CA1 region. In contrast, EA alleviated CPB induced cognitive impairment and activated PINK1-mediated mitophagy and restored hippocampal synaptic protein levels, which was reversed by PINK1 downregulation. These findings extend the understanding of EA's neuroprotective mechanisms by demonstrating a causal role for PINK1-dependent mitophagy in a CPB-induced POCD model, providing a mechanistic rationale for EA preconditioning in cardiac surgery settings.
    Keywords:  Electroacupuncture; Mitophagy; PINK1; Postoperative cognitive dysfunction; Synaptic plasticity
    DOI:  https://doi.org/10.1016/j.bbr.2026.116395
  22. Free Radic Biol Med. 2026 Jul 18. pii: S0891-5849(26)00958-5. [Epub ahead of print]255 307-318
    Dual-regulation of mitophagy and cytosolic mtDNA-induced inflammation for the treatment of inflammatory bone loss.
    Kaiwen Zheng, Benchi Che, Yongzhi Cui, Han Yang, Yu Xiang, Yanchun Gao, Pei Liu, Zhiyong Mu, Jinwu Wang, Yongjun Xia, Yuanyuan Guo, Dehao Fu.
      Inflammatory osteoporosis, also known as "immunoporosis," is a condition characterized by chronic inflammation and mitochondrial dysfunction, leading to impaired bone regeneration. Mitochondrial DNA (mtDNA) leakage activates the cGAS-STING pathway, triggering excessive inflammatory responses and hindering osteogenesis. Concurrently, defective mitophagy exacerbates mitochondrial damage, perpetuating a cycle of bone loss. This study investigated the role of the mtDNA-cGAS-STING axis in lipopolysaccharide (LPS)-induced bone marrow mesenchymal stem cells (BMSCs) dysfunction and inflammatory bone loss. We exposed BMSCs to LPS and assessed mitochondrial function, mtDNA release, and cGAS-STING activation using RT-qPCR, Western blotting, and immunofluorescence. We then engineered exosomes to co-deliver siRNA targeting STING and PINK1 mRNA, testing their effects on osteogenesis and mitochondrial homeostasis in vitro and in a mouse model of LPS-induced osteoporosis. LPS exposure resulted in mitochondrial damage, mtDNA leakage, and cGAS-STING activation, impairing osteogenic differentiation and increasing inflammatory cytokine expression. While STING inhibition reduced inflammatory signaling, it did not restore mitochondrial function, whereas PINK1 overexpression improved mitophagy and partially suppressed cGAS-STING activation. Dual regulation through siSTING/PINK1@Exo synergistically reduced mitochondrial ROS, restored membrane potential, promoted osteogenic marker expression, and enhanced mineralization in vitro. Dual-regulated exosomes significantly improved trabecular bone microarchitecture, reduced STING expression, and enhanced RUNX2 and OCN expression compared to single treatments in an in vivo model. These results demonstrate that combining mitophagy activation with STING inhibition via engineered exosomes offers a promising therapeutic strategy for inflammatory osteoporosis by addressing both mitochondrial dysfunction and chronic inflammation.
    Keywords:  Bone regeneration; Exosomes; Inflammatory bone loss; Mitophagy; cGAS–STING pathway
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.07.031
  23. iScience. 2026 Aug 21. 29(8): 116831
    Mitochondrial dynamics and antiviral responses in Atlantic salmon cardiomyocytes during piscine myocarditis virus infection.
    Antoni Malachowski, Deanna Lynn Wolfson, Randi Olsen, Alf Seljenes Dalum, Ida Sundvor Opstad, Krishna Agarwal, Roy Ambli Dalmo, Jaya Kumari Swain.
      Viral infections in higher vertebrates are known to remodel mitochondrial dynamics, which play a critical role in regulating immune responses, energy production and cellular homeostasis. Currently, understanding of mitochondrial dynamics during viral infection in teleost is limited. This study provides the first detailed investigation of mitochondrial responses to piscine myocarditis virus (PMCV) infection, the causative agent of cardiomyopathy syndrome (CMS) and a severe cardiac disease in Atlantic salmon causing economic losses in aquaculture. This study investigates the temporal effects of PMCV infection in cardiomyocytes on mitochondrial dynamics, associated molecular responses using fluorescence microscopy, transmission electron microscopy, histopathology and RT-qPCR. Distinct mitochondrial subpopulations with specific morphologies and spatial distributions were identified. PMCV infection induced marked mitochondrial remodeling, characterized by early fission, followed by swelling and elongation at peak viral RNA levels. These findings link viral kinetics and immune response to mitochondrial remodeling, providing mechanistic insight into CMS pathogenesis and cardiac health.
    Keywords:  Atlantic salmon; CMS; PMCV; antiviral response; cardiomyocytes; cardiomyopathy syndrome; mitochondria; piscine myocarditis virus
    DOI:  https://doi.org/10.1016/j.isci.2026.116831
  24. J Ethnopharmacol. 2026 Jul 20. pii: S0378-8741(26)01069-X. [Epub ahead of print]372 122215
    Mailuo Shutong pills alleviate limb swelling in femoral fracture rats by orchestrating mitophagic clearance and ferroptotic suppression.
    Xia Zhuang, Tingmei Mo, Wenjie Ji, Baohua Wang, Ru Yao, Wenxue Zhao, Lan Yang, Yan Xu, Yujun Tan, Jingchun Yao, Chenghong Sun, Guoliang Cheng.
       ETHNOPHARMACOLOGICAL RELEVANCE: Mailuo Shutong Pill (MLSTP) is a well-established formula developed by National Grand Master of Traditional Chinese Medicine Tang Zuxuan for treating thrombotic superficial phlebitis of the lower limbs. Clinically, it is commonly used for conditions caused by damp-heat and blood stasis obstructing the meridians, including thrombotic superficial phlebitis, subacute deep vein thrombosis, varicose veins, diabetic foot, as well as limb swelling and pain.
    AIM OF THE STUDY: Previous studies have demonstrated that MLSTP protected against limb swelling caused by femoral fracture (SCFF). This study further investigated the regulatory mechanisms of MLSTP on mitophagy and ferroptosis in the SCFF model, aiming to elucidate its multi-target pharmacological actions.
    MATERIALS AND METHODS: Male SD rats were subjected to a femoral fracture procedure to establish the SCFF model. Rats were randomly divided into Sham, Model, MLSTPL, MLSTPH, and Aescuven forte groups. Muscle pathology and iron deposition were assessed by hematoxylin-eosin (H&E) and Prussian blue staining. Muscle ATP, SOD, MDA, GSH, and CAT were assayed using Enzyme-linked immunosorbent assay (ELISA) kits. Proteomic analysis of muscle tissues was performed to identify differentially regulated signaling pathways. Mitochondrial morphology was observed by transmission electron microscopy (TEM). Mitophagy and ferroptosis-related proteins were assessed by immunofluorescence. Western blot analysis was performed to detect the expression of proteins related to the NRF2/HO-1/NQO1 pathway, NLRP3 inflammasome signaling, mitochondrial respiratory chain complexes, AMPK/mTOR axis, mitophagy, and ferroptosis.
    RESULTS: MLSTP ameliorated muscle pathology and reduced iron deposition in SCFF rats, while increasing ATP, SOD, GSH, and CAT levels and decreasing MDA content. Proteomic analysis associated its protective effect with oxidative phosphorylation. TEM revealed attenuated mitochondrial damage. Immunofluorescence and Western blot suggested that MLSTP activated NRF2/HO-1/NQO1, regulated respiratory chain components including NDUFB8, SDHB, UQCRC2, MTCO1, ATP5A, enhanced PINK1/Parkin-mediated mitophagy via AMPK/mTOR, and suppressed NLRP3 inflammasome and ferroptosis.
    CONCLUSIONS: This study demonstrates that MLSTP alleviates muscle swelling in SCFF rats by regulating the mitochondrial respiratory chain, ameliorating disordered mitophagy, and inhibiting ferroptosis. The present investigation provides a theoretical framework supporting the application of MLSTP for managing fracture-induced muscle edema.
    Keywords:  Ferroptosis; Mailuo Shutong pills; Mitochondrial respiratory; Mitophagy; Swelling caused by femoral fracture
    DOI:  https://doi.org/10.1016/j.jep.2026.122215
  25. Phytomedicine. 2026 Jul 14. pii: S0944-7113(26)00811-1. [Epub ahead of print]159 158580
    Salidroside ameliorated high-altitude exposure induced retinal ganglion cell death by activating HIF-1α/BNIP3 signaling mediated mitophagy and inhibiting ferroptosis.
    Cong Han, Yuting Li, Junyi Qiao, Xingxing Zheng, Qian Liu, Zhaoxiong Wang, Rui Yang, Yaping Meng, Wenfang Zhang, Yi Yang.
       BACKGROUND: The mechanism of retinal ganglion cells (RGCs) injury induced by high-altitude hypobaric hypoxic conditions remains unclear, and there are no effective treatment methods available. Salidroside (SAL) is an antioxidant drug, but its protective effect on hypobaric hypoxia induced RGCs injury remains unclear.
    OBJECTIVE: This study investigated the mechanisms underlying RGCs injury following acute high-altitude exposure (HAE) and the protective effects of SAL on RGCs, along with its underlying mechanisms.
    METHODS: We established a high-altitude hypobaric hypoxia exposure mouse model to evaluate the protective effect of SAL on RGCs. RNA sequencing and bioinformatics analysis were used for injury mechanism prediction and pathway enrichment. Western blot (WB), immunofluorescence (IF), optical coherence tomography (OCT), scotopic threshold reaction (STR) and transmission electron microscopy (TEM) were used to elucidate the protective effect of SAL.
    RESULTS: SAL treatment significantly improved the damage to RGCs caused by HAE. Mechanistically, SAL treatment significantly activated the mitophagy mediated by the HIF-1α/BNIP3 pathway, reduced the levels of Fe²⁺ and reactive oxygen species (ROS), and enhanced the expression of GPX4. Thus, it alleviated the ferroptosis caused by HAE in RGCs, maintaining the structure and function of RGCs.
    CONCLUSION: SAL demonstrates significant promise as a therapeutic agent for RGCs damage by enhancing protective mitophagy, reducing oxidative stress responses, and inhibiting ferroptosis in RGCs caused by HAE.
    Keywords:  Ferroptosis; High-altitude exposure; Mitophagy; Retinal ganglion cells; Salidroside
    DOI:  https://doi.org/10.1016/j.phymed.2026.158580
  26. Int J Biol Macromol. 2026 07 21. pii: S0141-8130(26)03514-2. [Epub ahead of print] 153569
    Retraction notice to "Molecular structure and protein function of mitochondrial fusion protein Mfn2 alleviate Alzheimer's disease: exercise assisted regulation" [Int. J. Biol. Macromol. 311 (2025) 143696].
    Hailei Li.
      
    DOI:  https://doi.org/10.1016/j.ijbiomac.2026.153569
  27. Stem Cell Res Ther. 2026 Jul 20.
    Miro1-mediated mitochondrial transfer boosts stem cell therapy for muscle atrophy via restoring mitochondrial homeostasis.
    Fangling Zhao, Jingxin Fu, Linli Gao, Mengting Zhou, Yuhui Xia, Zexian Zhao, MengNa Yang, Jiahui He, Wei Zhu, Mengxiong Pan, Kaiming Liu.
      Mitochondrial dysfunction underlies the major defect in muscle atrophy (characterized by the loss of skeletal muscle mass and function). Mesenchymal stem cells (MSCs), which can mediate mitochondrial transfer (MT) via tunneling nanotubes (TNTs), have been shown to exert therapeutic effects, yet the underlying mechanism remains unclear. Mitochondrial Rho GTPase 1 (Miro1) is crucial for regulating mitochondrial homeostasis; in this study, we aimed to investigate the roles of Miro1 and Milton in MSC-based therapy for muscle atrophy. Dexamethasone (DEX)-induced C2C12 cells and chronically aged mice were used as in vitro cellular and in vivo muscle atrophy models, respectively. In vitro experiments demonstrated that overexpression of Milton alone failed to enhance MT in DEX-induced C2C12 cells. Although Milton could promote the formation of TNTs, it was unable to drive mitochondrial movement along microtubules in the absence of Miro1.In contrast, Miro1 knockdown (MSCmiro1Lo) significantly reduced MT in vivo, while Miro1 overexpression (MSCmiro1Hi) improved mitochondrial morphology, increased muscle fiber count and cross-sectional area, upregulated the expression of type I/III collagen, and downregulated the expression of Atrogin1 and MURF1. Additionally, Miro1 overexpression ameliorated functional outcomes such as grip strength, running distance, and physical activity, and elevated the levels of proteins related to mitochondrial fusion, mitophagy, and biogenesis in damaged muscle cells. These findings indicate that Miro1 is a critical driver of MT, and Miro1-enhanced MT confers substantial in vivo therapeutic benefits. This study provides robust evidence supporting Miro1 as a potential target for the treatment of muscle atrophy-related disorders.
    Keywords:  Miro1; Mitochondrial homeostasis; Mitochondrial transfer; Muscle atrophy; Stem cells
    DOI:  https://doi.org/10.1186/s13287-026-05191-2
  28. Cell Signal. 2026 Jul 24. pii: S0898-6568(26)00420-1. [Epub ahead of print] 112763
    Impaired mitochondrial quality control and stress signalling machinery modulate senescence induction by genotoxic challenge.
    Mia Simons Weston, Marta Dominguez Prieto, Nicoleta Moisoi.
      Cellular senescence is a hallmark of ageing and age-related disease and is closely associated with mitochondrial dysfunction and the accumulation of DNA damage. However, the contribution of mitochondria-nucleus communication, mitochondrial quality control (mtQC) and stress signalling to senescence remains incompletely understood. Here, we investigated the interplay between mtQC pathways and cellular stress responses in DNA damage-induced senescence using mouse embryonic fibroblasts (MEFs). MEFs deficient in the mitochondrial protease HtrA2 (proteostasis), the transcription factor Chop (integrated stress response; ISR) or the mitophagy regulator Pink1 were exposed to three mechanistically distinct DNA-damaging agents: bleomycin, etoposide and doxorubicin. Senescence was characterised using multiple complementary markers, including the proportion of high senescence-associated β-galactosidase-positive cells, nuclear size, total and nuclear p21 abundance, and transcriptional analysis of p16, p21 and genes associated with cell-cycle regulation and stress signalling. Mitochondrial dysfunction through mtQC impairment enhanced sensitivity to senescence with HtrA2 and Pink1 loss promoting increased senescence under DNA damage. Although DNA damage response (DDR) was activated as seen by changes in p21 homeostasis, this did not always correlate with senescence levels, which indicates that DDR alone cannot account for all senescence characteristics. The ISR played a modulatory role in the senescence induction, with Chop loss of function reducing senescence induction following DNA damage despite DDR activation. The different DNA damaging drugs produced different senescence outcomes, thus highlighting the importance of the stressor context in addition to the cellular homeostasis mechanisms in the overall senescence profile. This approach allowed, for the first time, to identify senescence subtypes dependent of mtQC and ISR integrity in the context of genotoxic stress.
    Keywords:  Genotoxic stress; Integrated stress response; Mitochondria quality control; Senescence subtypes
    DOI:  https://doi.org/10.1016/j.cellsig.2026.112763
  29. Exploration (Beijing). 2026 Jul 10. 20250125
    Artificial Chlorella Biohybrids for Alleviation of Cartilage Degeneration in Osteoarthritis.
    Yongyun Chang, Keyu Kong, Minghao Jin, Shasha Liu, Yangzi Yang, Yingchun Zhu, Hua Qiao, Wenxuan Fan, Xinru Wu, Jingwei Zhang, Yansong Qi, Yongsheng Xu, Xiang Feng, Pingcuo Nima, Piting Ji, Tariel Mamuladze, Andrei A Korytkin, Huiwu Li, Jingke Fu, Zanjing Zhai.
      Osteoarthritis (OA), one of the most common chronic joint diseases, is characterised by cartilage imbalance and disruption of the cartilage extracellular matrix. In this study, we observed impaired mitophagy and glucose metabolism disorders in OA chondrocytes, which exacerbated cartilage degeneration. And we unveil Chlorella, a natural microorganism that appeared more than two billion years ago, as an efficient regulator of both mitophagy and glucose metabolism in OA chondrocytes. Chlorella activates mitophagy and rescues mitochondrial function. More importantly, Chlorella inhibits glycolysis and reprograms glucose metabolism in chondrocytes, leading to the remodelling of chondrocyte homeostasis and alleviation of cartilage degeneration both in vitro and in vivo. As a proof of concept, we constructed a photothermal Chlorella biohybrid (Ch@P) that induced articular thermal stimulation under near-infrared irradiation and significantly strengthened the protection against cartilage degeneration in DMM mouse models of OA. Ch@P activates the AMPK-Sirt1 signalling pathway to restore mitochondrial homeostasis and energy metabolism in chondrocytes. Furthermore, HSP70 is also activated to regulate chondrocyte homeostasis due to articular thermal stimulation. Our study unveils the activity of natural Chlorella in chondrocyte homeostasis by activating mitophagy and reprogramming glucose metabolism and identifies an artificial Chlorella biohybrid as a promising therapeutic option for OA treatment.
    Keywords:  cartilage degeneration; chondrocytes; glycolysis; mitophagy; osteoarthritis
    DOI:  https://doi.org/10.1002/EXP.20250125
  30. Cell Commun Signal. 2026 Jul 22.
    DRP1 lysine 616 lactylation exacerbates cerebral ischemia-reperfusion injury by activating the STING inflammatory pathway.
    Xiaoqi Ma, Dan Xin, Xianjia Li, Zhenhao Ying, Zifeng Li, Wenli Wang, Zhigang Mei, Jinwen Ge.
      Ischemia-hypoxia-induced inflammation and glycolysis are linked to the severity of cerebral ischemia-reperfusion injury (CIRI), but the mechanisms are unclear. Current research suggests that the inflammatory response of immune cells activated by STING is a key regulatory molecule in cellular inflammatory damage. However, the specific mechanisms underlying STING-mediated CIRI inflammatory responses remain unclear. This study found that STING expression was specifically elevated in microglia in the damaged side of the hippocampus in CIRI model mice, and this elevation was positively correlated with the severity of CIRI. Our previous research indicated that the dynamic process of mitochondrial fusion and fission is closely associated with CIRI. Building on this, we integrated glycolysis, mitochondrial fission, and the STING inflammatory pathway. Mechanistically, our data suggest that DRP1 K616 is a critical candidate site involved in DRP1 lactylation-associated regulation, which promotes STING pathway activation and contributes to the progression of CIRI. In conclusion, our findings offer substantial evidence that lactate-driven DRP1-mediated mitochondrial fission facilitates the involvement of the STING inflammatory pathway in CIRI. These results suggest that modulating lactate metabolism may serve as a crucial upstream strategy for therapeutic intervention in CIRI.
    Keywords:  DRP1; Ischemic stroke; Lactylation; Microglia; Mitochondrial fission; cGAS-STING pathway
    DOI:  https://doi.org/10.1186/s12964-026-03093-7
  31. Mol Cell Biochem. 2026 Jul 20.
    Trimethylamine N-oxide activates cardiac fibroblasts transformation through NLRP3 inflammasome activation with changes in mitochondrial dynamics and ER-mitochondrial contact under ER stress.
    Huimin Wang, Hanlin Liu, Xinnan Meng, Jiantao Song, Yan Jin, Yuanyuan Bai.
      Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been linked to cardiovascular diseases. This study aimed to explore the role of TMAO in cardiac fibrosis by examining its effects on the NLRP3 inflammasome, endoplasmic reticulum stress (ERS), mitochondria-associated membranes (MAMs), and mitochondrial dynamics in cardiac fibroblasts (CFs), alongside clinical data from acute myocardial infarction (AMI) patients and unstable angina (UA) patients and AMI animal model data. Plasma TMAO levels were measured in AMI patients and healthy controls. In vitro, CFs were treated with TMAO to assess cellular activation and fibrosis markers. Western blot, immunofluorescence, and RNA sequencing identified key pathways and proteins related to ERS, NLRP3 inflammasome activation, and mitochondrial dynamics. In vivo, Masson's trichrome staining, Hematoxylin-Eosin (HE) staining and Immunohistochemical were used to evaluate the effects of TMAO on AMI mice. Plasma TMAO levels were significantly higher in the AMI group. TMAO promoted cardiac fibroblast activation and fibrosis by increasing α-SMA and Collagen I expression. It induced ERS, marked by elevated GRP78, p-PERK, and CHOP, and upregulated Sigma-1R, enhancing MAM formation. TMAO also altered mitochondrial dynamics via DRP1 phosphorylation and Mfn2 expression. RNA sequencing identified macrophage migration inhibitory factor (MIF) as a key mediator linking TMAO to NLRP3 inflammasome activation. TMAO exacerbates myocardial injury and fibrotic remodeling in AMI mice. TMAO exacerbates cardiac fibrosis via ERS and NLRP3 activation, with implications for mitochondrial dynamics and MAM formation. Elevated TMAO levels in AMI patients underscore its potential as a therapeutic target for ventricular remodeling fibrosis.
    Keywords:  Cardiac fibroblasts; Endoplasmic reticulum stress; MAMs; MIF; NLRP3; TMAO
    DOI:  https://doi.org/10.1007/s11010-026-05658-z
  32. J Control Release. 2026 Jul 18. pii: S0168-3659(26)00595-X. [Epub ahead of print]397 115192
    Nanozyme-integrated hydrogel orchestrates mitochondrial quality control to counter inflammatory and oxidative milieu during disc degeneration.
    Zhiwei Liao, Guoqiang Yin, Jingpei Liu, Yuhao Sun, Hongchuan Wang, Shuai Li, Cao Yang.
      Intervertebral disc degeneration (IDD) is a major cause of low back pain, driven by nucleus pulposus (NP) cell dysfunction, excessive reactive oxygen species (ROS), and chronic inflammation. Current biomaterial-based strategies often fail to simultaneously address oxidative stress and inflammatory signaling in a sustained and synergistic manner. Here, we develop a thermosensitive Pluronic F127-based composite hydrogel co-delivering a tannic acid‑cerium nanozyme and the FPR1 antagonist HCH6-1. The hydrogel undergoes sol-gel transition at body temperature, enabling minimally invasive injection and sustained local release in the intervertebral disc. The cerium nanozyme exerts potent ROS-scavenging activity, effectively reducing intracellular ROS levels and upregulating the antioxidant protein TXNRD1. Meanwhile, HCH6-1 specifically antagonizes FPR1, thereby suppressing cGAS-STING pathway activation and suppressing downstream inflammatory cascades. Beyond direct anti-inflammatory effects, this system significantly enhances mitophagy activity in NP cells, facilitating the clearance of dysfunctional mitochondria and restoring autophagic flux. Collectively, in vitro and in vivo evidence confirms that this dual-functional hydrogel attenuates NP cell inflammation and significantly retards the progression of IDD. Thus, this injectable and biocompatible platform offers a synergistic strategy that couples nanozyme-mediated antioxidant therapy with targeted FPR1 blockade, holding substantial promise for intervertebral disc repair.
    Keywords:  Cerium nanozyme; FPR1 antagonist; Intervertebral disc degeneration; Mitophagy; Thermosensitive hydrogel
    DOI:  https://doi.org/10.1016/j.jconrel.2026.115192
  33. Mol Biomed. 2026 Jul 22. pii: 117. [Epub ahead of print]7(1):
    SelO-mediated NAD+ hydrolysis safeguards mitochondrial homeostasis.
    Tong Yao, Shuai Wang, Fangfang Zhou.
      
    DOI:  https://doi.org/10.1186/s43556-026-00509-1
  34. Front Immunol. 2026 ;17 1832261
    M2 macrophage-derived exosomes improves secondary lymphedema through cellular mitochondrial homeostasis regulation via the Keap1-Nrf2/mPTP axis.
    Jinli Ma, Luya Pu, Yundong Zhang, Baiao Wu, Rui Fei, Dongmei Han, Miao Hao, Jianshi Du.
       Background: Secondary lymphedema leads to progressive tissue remodeling and immune dysregulation. Dysregulation of macrophage polarization critically influences pathological progression. Oxidative stress and mitochondrial homeostasis are the critical components of secondary lymphedema.
    Methods: A secondary lymphedema model and an LPS-induced in vitro cell injury model were established. Mitochondrial dynamics were evaluated using the ROS assay, mitochondrial membrane potential analysis and mPTP opening assays. Mechanistic investigations included Nrf2 nuclear translocation analysis via immunofluorescence, western blotting, and pharmacological inhibition of exosome biogenesis using GW4869.
    Results: Secondary lymphedema tissues exhibited a significant imbalance in M1/M2 macrophage infiltration (with an increase in M1 and decrease in M2), along with elevated IL-1β levels. M2-Exo significantly prevents the proliferation, migration, and tube formation of human lymphatic endothelial cells and alleviated the mitochondrial damage induced by LPS. This mechanism may involve activation of Keap1-Nrf2 signaling.
    Conclusion: M2 macrophage exosomes activated the Nrf2 anti-oxidative stress pathway. This activation improves mitochondrial homeostasis and enhances the function of human lymphatic endothelial cells by delivering active ingredients, offering a new strategy for the treatment of secondary lymphedema.
    Keywords:  Nrf2; exosome; macrophage polarization; mitochondrial permeability transition pore; secondary lymphedema
    DOI:  https://doi.org/10.3389/fimmu.2026.1832261
  35. Autophagy. 2026 Jul 23. 1-26
    CX3CR1+ macrophages aggravate doxorubicin-induced cardiomyopathy by impairing cardiac mitophagy via the CSF1R-PARP1-IL1B axis.
    Yiping Shi, Long Chen, Yuxiao Feng, Jingtao Liu, Wendi Wu, Yawei Jin, Huan Tong, Yijie Huang, Yiming Li, Zhaokuan Li, Guo Zhou, Ben He, Yu Wang, Qin Shao.
      Doxorubicin is a widely used chemotherapeutic agent, but its clinical application is hindered by severe cardiotoxicity. Among immune cells, Cx3cr1+ macrophages have emerged as key regulators of cardiovascular disease, with their development and maturation tightly controlled by CSF1R (colony stimulating factor 1 receptor). Using multi-omics sequencing, we observed a marked expansion of Cx3cr1+ macrophages in doxorubicin-induced cardiomyopathy, yet their precise functional role in this pathological process has remained elusive. This study employed various genetically modified mouse models, including cell depletion models, lineage tracing models, and conditional gene knockout models targeting Cx3cr1+ macrophages, alongside transcriptomic sequencing, proteomic profiling, and multi-level in vivo and in vitro experiments to elucidate the role and mechanisms of Cx3cr1+ macrophages and their receptor CSF1R in doxorubicin-induced cardiac injury. We found that Cx3cr1+ macrophages are significantly enriched in hearts affected by doxorubicin-induced cardiomyopathy, and their depletion notably improves cardiac function. Further investigation revealed that in these macrophages, CSF1R competitively binds to the E3 ubiquitin ligase NEDD4, thereby inhibiting the ubiquitination and degradation of PARP1. This process promotes inflammasome activation and pyroptosis, driving massive IL1B secretion. IL1B directly suppresses cardiomyocyte mitophagy, disrupts energy metabolic homeostasis, and ultimately leads to cardiac dysfunction. Notably, the use of the CSF1R inhibitor PLX3397 or an IL1B-neutralizing antibody effectively halted these pathological processes and significantly improved cardiac function. In summary, this study unveils a novel mechanism through which Cx3cr1+ macrophages regulate cardiomyocyte function via the CSF1R-PARP1-IL1B-mitophagy signaling axis, providing a new theoretical foundation and intervention strategy for doxorubicin-induced cardiomyopathy targeted therapy.Abbreviations: BMDM: bone marrow-derived macrophages; CKMB: creatine kinase MB isoenzyme; CSF1R: colony stimulating factor 1 receptor; csf1r-cKO: csf1r conditional knockout; DIC: doxorubicin-induced cardiomyopathy; DOX: doxorubicin; HE: hematoxylin and eosin; HW:TL: heart weight:tibial length; LDH: lactate dehydrogenase; MAP1LC3/LC3: microtuble-associated protein 1 light chain 3; NPPA: natriuretic peptide type A; PI: propidium iodide; PYCARD/ASC: PYD and CARD domain containing; TNNT2/cTnT: troponin T2, cardiac; WGA: wheat germ agglutinin.
    Keywords:  CSF1R; Cx3cr1+ macrophage; doxorubicin-induced cardiomyopathy; mitophagy; pyroptosis
    DOI:  https://doi.org/10.1080/15548627.2026.2702870
  36. Proc Natl Acad Sci U S A. 2026 Jul 28. 123(30): e2603069123
    VAMP7-dependent mitochondria-lysosome contacts contribute to glial mitochondrial dynamics and dopaminergic neuron survival.
    Honglei Wang, Mengxiao Wang, Yu-Ting Tsai, Yi-Hsuan Cheng, Yu-Tung Lin, Chia-Ching Lin, Yi-Hua Lee, Linfang Wang, Shuanglong Yi, Shiping Zhang, Yufeng Pan, Margaret S Ho.
      Although disrupted mitochondrial dynamics in neurons are closely linked to neurodegenerative diseases, far less is known about how mitochondrial dynamics are regulated in glia or whether glial mitochondrial dysfunction contributes to neurodegeneration. Here, we show that the R-SNARE protein VAMP7 regulates the untethering of mitochondria-lysosome contacts (MLCs) in adult fly glia. Glial-specific knockdown of VAMP7 leads to prolonged MLCs and mitochondrial elongation associated with altered fission/fusion dynamics. These VAMP7-deficient mitochondria exhibit hyperpolarized membrane potential, leading to increased reactive oxygen species production, lipid droplet accumulation, and dopaminergic neurodegeneration. Mechanistically, VAMP7 interacts with the GTPase-activating protein TBC1D15-17 to promote Rab7 GTP hydrolysis. Without VAMP7, TBC1D15-17 remains bound to Rab7 but fails to activate its hydrolysis, resulting in elevated GTP-bound Rab7 and impaired MLCs untethering. Consistently, expression of GTP-locked Rab7Q67L or GTPase-activating protein-dead TBC1D15-17ΔGAP phenocopies the mitochondrial defects, while GDP-bound Rab7T22N or wild-type TBC1D15-17 restores the MLC dynamics. Considering that SNARE proteins mediate membrane fusion, our results demonstrate a role for VAMP7 in glial mitochondrial dynamics via organelle contacts, impacting neuron survival in a non-cell-autonomous manner.
    Keywords:  VAMP7; glia; mitochondrial dynamics
    DOI:  https://doi.org/10.1073/pnas.2603069123
  37. Hypertension. 2026 Jul 20.
    Fibroblast S1PR2 Amplifies NLRP3 Inflammasome Activation Under Pressure Overload.
    Caixia Zhou, Zhihao Liu, Zhiru Wang, Zekun Cui, Qian Wang, Xiaoyan Fang, Xiaoli Chen, Jie Liu, Yuzhen Zhang, Huaming Cao, Jinjin Wu, Lin Zhang.
       BACKGROUND: Although NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasome activation has been implicated in pressure overload-induced cardiac hypertrophy, inflammation, and heart failure, prior studies have focused primarily on cardiomyocytes and immune cells. The potential contribution of cardiac fibroblasts to NLRP3 inflammasome activation under pressure overload remains poorly defined. Here, we investigated the role of cardiac fibroblasts in NLRP3 inflammasome activation and sought to identify its key upstream regulator in the pressure-overloaded heart.
    METHODS: We analyzed single-cell transcriptomic data set of human and murine hearts, together with fibroblast-specific Nlrp3-knockout mice and S1pr2 loss- and gain-of-function mouse models. Transverse aortic constriction was used to induce pressure overload.
    RESULTS: We identified cardiac fibroblasts as the principal effectors of NLRP3 inflammasome activation under pressure overload. NLRP3 deficiency in fibroblasts markedly attenuated cardiac hypertrophy and inflammation under pressure overload. We further found that S1PR2 (sphingosine-1-phosphate receptor 2) is a critical upstream regulator of fibroblast NLRP3 inflammasome activation. Fibroblast-specific S1PR2 deletion suppressed inflammasome activation, mitigated hypertrophy, and preserved cardiac function, whereas S1PR2 overexpression in fibroblasts exacerbated these pathological changes under pressure overload. Further analyses revealed that S1PR2/ROCK (rho-associated coiled-coil-containing protein kinase) signaling augments DRP1 (dynamin-related protein 1)-dependent mitochondrial fission while suppressing Parkin-mediated mitophagy, thereby promoting mitochondrial damage and mitochondrial DNA leakage, which in turn culminate in NLRP3 inflammasome activation.
    CONCLUSIONS: This study provides in vivo evidence that cardiac fibroblasts constitute a major source of NLRP3 inflammasome activation in response to pressure overload. Fibroblast S1PR2 signaling links mitochondrial dysfunction to inflammasome activation, revealing a novel proinflammatory axis that exacerbates pressure overload-induced heart failure.
    Keywords:  animals; fibroblasts; heart failure; inflammation; mitophagy
    DOI:  https://doi.org/10.1161/HYPERTENSIONAHA.126.27475
  38. Histol Histopathol. 2026 Jul 14. 25129
    FGF20 relieves high glucose-induced Schwann cell mitochondrial damage through the activation of SIRT1.
    Ya Ning, Yuewei Liang, Youqing Huang.
       BACKGROUND: Schwann cell mitochondrial damage plays an important role in diabetic neuropathic pain (DNP). Fibroblast growth factor 20 (FGF20) has been shown to protect nerve cells and regulate neural function, but its function and mechanism in DNP remain unclear.
    METHODS: A DNP mouse model induced by streptozotocin (STZ) and an RSC96 cell model induced by high glucose (HG) were used for experimental studies. The metabolism of the mice was evaluated by measuring body weight and blood glucose levels. Pathological changes in the sciatic nerve were observed by hematoxylin and eosin (HE) staining. The pain sensitivity of the mice was evaluated by the von Frey test and thermal sensitivity test. Cell viability was determined by a cell counting kit-8 (CCK-8) assay. MitoSOX Red staining was performed to detect mitochondrial reactive oxygen species (ROS) levels. 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining was used to measure the mitochondrial membrane potential, and the expression of proteins was detected by western blotting and immunohistochemistry.
    RESULTS: FGF20 expression was low in DNP mice and HG-induced Schwann cells. Overexpression of FGF20 relieved symptoms in DNP mice, including partial recovery of body weight, a reduction in blood glucose levels, an increase in the tactile response threshold, and a reduction in thermal response delay. In addition, FGF20 overexpression increased the expression of the mitochondrial autophagy proteins PINK1 and Parkin, adenosine triphosphate (ATP) content, and mitochondrial membrane potential levels, and reduced ROS accumulation in RSC96 cells. Molecular mechanisms reveal that sirtuin 1 (SIRT1) expression is downregulated in DNP, and FGF20 upregulates SIRT1 expression, and that SIRT1 knockdown weakened the improvement effect of FGF20 on mitochondrial autophagy and damage.
    CONCLUSION: FGF20 may promote mitochondrial autophagy in Schwann cells by upregulating SIRT1 expression, thereby inhibiting mitochondrial damage and thus alleviating DNP.
    DOI:  https://doi.org/10.14670/HH-25-129
  39. Cell Death Dis. 2026 Jul 18.
    Tubular tRF‑1:30‑Gln‑CTG‑4 attenuates tubulointerstitial fibrosis by mitigating FBXO7-mediated mitophagy defect in diabetic kidney disease.
    Jia-Ling Ji, Yun-Yang Qiao, Jia-Yue Sun, Ying Huo, Hui-Min Shi, Gao-Ting Qu, Shan-Wen Li, Chan Huang, Yu Feng, Pei Zhang, Ling Ding, Zuo-Lin Li, Ai-Qing Zhang.
      Tubulointerstitial fibrosis (TIF) is a crucial pathological feature and inevitable consequence of progressive diabetic kidney disease (DKD). Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNA by cleavage of tRNAs, have recently attracted attention due to their functional significance in diverse biological processes. However, the role of tRFs in TIF is largely elusive. In the present study, we found that a tRF, tRF‑1:30‑Gln‑CTG‑4, was markedly decreased in proximal renal tubules and highly correlated with TIF in DKD mice. The overexpression of tRF‑1:30‑Gln‑CTG‑4 revealed a therapeutic effect against TIF. Further, RNA pull-down and RNA-immunoprecipitation assay were performed to identify that FBXO7, an adaptor protein in the SCF E3 ligase complex, was the targeted protein of tRF‑1:30‑Gln‑CTG‑4. Mass spectrometry and co-immunoprecipitation experiments revealed that PINK1, a master mitophagy-regulating protein, acted as the substrate of FBXO7 in tubular epithelial cells. Mechanistically, elevated FBXO7 promoted mitophagy defect through mediating PINK1 ubiquitylation and proteasomal degradation. The overexpression of tRF‑1:30‑Gln‑CTG‑4 alleviated defective mitophagy. Taken together, this study not only represents a novel insight into the pathogenesis of TIF but also provides a promising therapeutic targeting for the delaying the progression of DKD.
    DOI:  https://doi.org/10.1038/s41419-026-09112-2
  40. Proc Natl Acad Sci U S A. 2026 Jul 28. 123(30): e2528979123
    HSP90α lactylation orchestrates PGC1α and LRPGC1 nuclear translocation driving mitochondrial biogenesis.
    Gang Wu, Hongmin Li, Tong He, Min Chen, Xiaoyu Jiang, Mengli Wei, Lei Zhou, Chengyu Li, Jingli Tao, Zhaojun Liu, Ming Shen, Honglin Liu.
      Mitochondrial biogenesis is a fundamental process that ensures energy supply and supports steroidogenesis in ovarian cells. Lactate has recently been identified as a signaling metabolite that promotes mitochondrial biogenesis; however, the underlying regulatory mechanisms remain poorly defined. Here, we identify Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90α) lactylation as a key mediator that links glycolytic metabolism to mitochondrial function. Specifically, lactylation of HSP90α at K58 recruits ULK1, thereby enhancing phosphorylation at S39; lactylation at K616 prevents CDK5-mediated phosphorylation at S596. This dual regulation facilitates the nuclear translocation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and its isoform LRPGC1, which activate NRF1/2-dependent transcription of mitochondrial biogenesis genes, such as Tfb1m, Tfb2m, and Tfam. Functionally, mitochondrial mass expansion both enhances cellular energy metabolism and promotes cholesterol import into mitochondria, thereby driving estrogen biosynthesis. Together, these findings reveal a lactate-HSP90α-PGC1α/LRPGC1 axis that metabolically couples glycolysis to mitochondrial biogenesis and reproductive hormone production, providing insights into the epigenetic regulation of follicular development.
    Keywords:  CDK5; HSP90α lactylation; HSP90α phosphorylation; PGC1α/LRPGC1; ULK1
    DOI:  https://doi.org/10.1073/pnas.2528979123
  41. Curr Neuropharmacol. 2026 Jul 13.
    Naotaifang Formula Suppresses Ferroptosis by Ameliorating Mitochondrial Biogenesis Through the Nrf2/TFAM Pathway in Ischemic Stroke.
    Mengzhen Wei, Danhong Liu, Qiusi Du, Zhigang Mei, Jun Liao.
       INTRODUCTION: This study aimed to investigate whether activating the Nrf2/TFAM pathway boosts mitochondrial biogenesis, reduces ferroptosis in ischemic stroke (IS), and evaluates Naotaifang (NTF) formula's therapeutic potential.
    METHODS: Ferroptosis and mitochondrial biogenesis indicators were measured at various time points following MCAO. Various methods, including transmission electron microscopy, immunofluorescence assay, enzyme-linked immunosorbent assay, Western blotting assays, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), were employed to evaluate the impact of NTF on mitochondrial biogenesis and ferroptosis in vivo and in vitro.
    RESULTS: IS significantly inhibits mitochondrial biogenesis and increases neuronal ferroptosis, with brain damage worsening over time. MCAO groups showed reduced expression of Nrf2, TFAM, ATP, CISD2, FPN, GPX4, SOD, and HO-1, alongside elevated Fe²⁺, ROS, and LPO (P < 0.05) compared to the control group. Both sulforaphane and NTF treatment reversed these effects; NTF treatment effectively increased the expression of Nrf2, TFAM, FtMt, CISD1, CISD2, FPN, and GPX4 while inhibiting the levels of Fe2+, ROS, and LPO. (P < 0.05).
    DISCUSSION: This finding clarifies mitochondrial biogenesis's crucial role, proposes a new "pathway + molecule" strategy for IS treatment, and supports NTF's clinical potential, though larger animal models and long-term safety studies are needed.
    CONCLUSION: In the context of IS, reduced mitochondrial biogenesis plays an important role in ferroptosis. Targeting the Nrf2/TFAM signaling pathway may improve mitochondrial biogenesis in IS. Furthermore, NTF can mitigate ferroptosis by promoting mitochondrial biogenesis through the Nrf2/TFAM signaling pathway.
    Keywords:  Naotaifang; Nrf2/TFAM pathway; ferroptosis; hypoxia.; ischemic stroke; mitochondrial biogenesis
    DOI:  https://doi.org/10.2174/011570159X443328260518223310
  42. Iran J Biotechnol. 2026 Jul;pii: e4296. [Epub ahead of print]24(3):
    Screening of Biomarkers Related to Mitophagy in Severe Pancreatitis Based on Bioinformatics Methods.
    Jiajia Li, Jinxin Cao, Zhipeng Wu, Wenjie Qi, Yingmin Ma.
       Objectives: This study aimed to identify mitophagy-related biomarkers in severe acute pancreatitis through integrated bioinformatics and machine-learning approaches, and to elucidate their potential regulatory mechanisms and diagnostic value.
    Materials and Methods: Differentially expressed genes (DEGs) related to SAP were screened based on the GSE194331 dataset (human whole blood samples), and candidate genes were obtained by taking the intersection with the mitophagy gene set. Key genes were screened by combining the least absolute shrinkage and selection operator (LASSO) regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms; the diagnostic efficacy was evaluated using the ROC curve, and a nomogram model was constructed. Furthermore, gene functions and regulatory mechanisms were revealed through Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), immune infiltration analysis, and ceRNA network, and potential targeted drugs were predicted using molecular docking.
    Results: A total of 16 DEGs related to mitophagy were identified. Functional enrichment analysis showed that they were significantly associated with metabolic and immune regulation pathways. Machine learning and expression level validation jointly screened PGD and LMNB1 genes as two key genes. The key genes showed significant expression differences in the training set and external validation set (upregulated in the SAP group), and had excellent diagnostic efficacy (area under the curve (AUC) > 0.85). Immune infiltration analysis showed that the infiltration of 13 types of immune cells increased in the SAP group, and PGD was highly positively correlated with immune cells such as activated dendritic cells (r = 0.82). Molecular docking indicated that estradiol and progesterone might target and regulate PGD and LMNB1.
    Conclusion: PGD and LMNB1 are key genes related to mitophagy in SAP and have excellent diagnostic value. This study provides a theoretical basis for the analysis of the molecular mechanism of SAP and the development of precise diagnosis and treatment strategies.
    Keywords:   GSEA; Immune infiltration; Mitophagy; Molecular docking; Severe acute pancreatitis; machine learning
    DOI:  https://doi.org/10.30498/ijb.2026.559698.4296
  43. Redox Biol. 2026 Jul 18. pii: S2213-2317(26)00315-0. [Epub ahead of print]96 104316
    Calcium-dependent redox signaling connects mitochondrial remodeling with PAD-associated NETosis during respiratory mycoplasma infection.
    Shun Wang, Weiqi Liu, Fuhua Gu, Jian Wang, Yuquan Guo, Liyang Guo, Yifan Li, Kexin Wang, Jie Zhang, Yecheng Yao, Zhiyong Wu, Jichang Li.
      Neutrophil extracellular trap (NET) formation is controlled by redox signaling and mitochondrial stress, but the connection between pathogen-induced Ca2+ influx, mitochondrial remodeling, and PAD-associated chromatin execution remains insufficiently defined. Using Mycoplasma gallisepticum (MG) as a model of respiratory mycoplasma infection, we examined how pathogen-activated redox signaling modulates NET formation and the subsequent fate of extracellular DNA. In neutrophils, MG promoted NET formation, although visible trap deposition was partly obscured by MG-associated nuclease activity. Early proteomic analysis indicated enrichment of calcium signaling, ROS-related pathways, autophagy/mitophagy, lysosome/phagosome programs, and MAPK-linked responses. Mechanistically, MG-induced NETosis was mediated through involved a Ca2+/ROS-associated program, in which mitochondrial dysfunction and mitophagy-related remodeling facilitated PAD3 nuclear redistribution, histone citrullination, and extracellular DNA release. In agreement with a supportive rather than exclusive function, mitophagy activation enhanced NET-associated responses, whereas mitophagy inhibition weakened but did not completely prevent MG-induced NET release. MG-associated nuclease activity digested extracellular traps, enabled MG to acquire DNA signals derived from digested trap structures, and lowered NET-dependent inflammatory activation in recipient macrophages and epithelial cells. In vivo, MG infection caused local NET-related responses and systemic neutrophil priming, linked to mainly associated with ROS/MAPK activation rather than prolonged mitophagy-related alterations. MG-Escherichia coli co-infection intensified inflammatory pathology, whereas DNase I produced partial protection. These results support a context-dependent model in which MG stimulates Ca2+-dependent redox signaling and mitochondrial remodeling, thereby contributing to PAD-associated NETosis, while pathogen nuclease activity modifies extracellular NET DNA fate and downstream inflammatory pathology.
    Keywords:  Calcium signaling; Mitophagy; Mycoplasma gallisepticum; Neutrophil extracellular traps; Redox signaling
    DOI:  https://doi.org/10.1016/j.redox.2026.104316
  44. Front Immunol. 2026 ;17 1884498
    Mitochondrial reprogramming in cervical cancer: crosstalk with tumor immunity, HPV oncogenic signaling, and therapeutic resistance.
    Li Pan, Peng Zhang, Dan Zhang, Gang Wang.
      Cervical cancer remains a major malignancy in women worldwide despite advances in human papillomavirus (HPV) vaccination, screening, and multimodal treatment. Persistent high-risk HPV infection is the principal driver of cervical carcinogenesis, yet viral oncogenesis alone cannot fully explain tumor progression, immune escape, and therapeutic failure. Increasing evidence suggests that mitochondrial reprogramming is a critical adaptive process that links HPV-driven transformation to metabolic plasticity, tumor immunity, and resistance to therapy. Beyond their canonical role in ATP production, mitochondria regulate redox homeostasis, mitochondrial dynamics, mitophagy, apoptotic priming, and mitochondria-derived danger signaling, thereby shaping both tumor-cell fitness and the surrounding immune microenvironment. In cervical cancer, HPV-associated oncogenic signaling promotes metabolic and mitochondrial remodeling, while downstream mitochondrial processes help sustain malignant growth, buffer oxidative and therapeutic stress, and influence immune responsiveness. Emerging studies further indicate that mitochondrial stress signals, particularly mitochondrial DNA-mediated innate immune activation, may connect tumor metabolism with anti-tumor immunity and immunotherapeutic sensitivity. At the same time, mitochondrial respiration, redox adaptation, and quality-control mechanisms contribute to chemoresistance and broader treatment tolerance. In this review, we summarize current evidence on how HPV oncogenic signaling reshapes mitochondrial biology in cervical cancer and discuss how mitochondrial reprogramming influences tumor immunity, immune evasion, and therapeutic resistance. We also highlight emerging mitochondria-targeted strategies and propose future directions for mechanistic and translational research. Together, these insights position mitochondrial reprogramming as both a conceptual framework and a potential therapeutic vulnerability in cervical cancer.
    Keywords:  HPV; cervical cancer; mitochondria; therapeutic resistance; tumor immunity
    DOI:  https://doi.org/10.3389/fimmu.2026.1884498
  45. J Appl Physiol (1985). 2026 Jul 20.
    Effects of 8-Week Exercise Snacks on Muscle Oxygenation and Cardiometabolic, Mitochondrial and Subclinical Atherosclerosis Markers in Sedentary Women.
    Omar A Hernández-López, Alejandro Martínez-Lucas, Alberto Hermo-Argibay, Julia Cacace, Clara Luna-Marco, Rodrigo Yañez-Sepulveda, Pablo Fernández-Collazo, Laura Perea-Galera, Celia Bañuls, Carlos Morillas, Milagros Rocha, Víctor M Víctor, Susana Rovira-Llopis.
      "Exercise snacks" (ExS) are brief, structured bouts of physical activity designed to counteract the metabolic effects of sedentary behavior. This pilot study examined whether ExS improves metabolic markers, body composition, fitness inidcators, PBMC mitochondrial dynamics, autophagy, and subclinical atherosclerosis. Twenty-two women (11 physically active [PA], 11 sedentary; IPAQ-classified) were enrolled. Sedentary participants completed daily 12-minute ExS sessions for 8 weeks. Assessments included body composition, blood biomarkers, muscle oxygenation, cardiorespiratory fitness, grip-strength, PBMC mitochondrial dynamics/autophagy markers, and neutrophil-endothelial interactions. Age-adjusted comparisons revealed that sedentary women (34±9 years) had similar body composition to PA participants (26±5 years). Cholesterol, LDL, and antioxidant capacity were reduced in sedentary women (p< 0.05). ExS reduced insulin (p< 0.01). Sedentary women displayed higher resting and maximal heart rates, lower estimated VO2max, and reduced muscle re-oxygenation vs PA (p< 0.05), all of which improved after ExS, though resting heart rate remained elevated vs PA (p< 0.01). Grip-strength was comparable between sedentary and PA women and increased after ExS (p< 0.01). Neutrophil-rolling velocity was decreased in sedentary vs PA (p< 0.01) and restored by ExS (p< 0.05). Expression of mitochondrial dynamics-related genes (mitofusins, OPA1, FIS1) was lower in sedentary vs PA (p< 0.05) without changes in protein levels. Autophagy and mitophagy-related genes (Beclin1, LC3b, p62, Pink/Parkin) were downregulated in sedentary vs PA (p< 0.05), while only LC3b mRNA and BECLIN1 protein increased after ExS (p< 0.01). Our findings indicate that ExS can improve cardiometabolic health, functional fitness, PBMC mitochondrial markers, and neutrophil-rolling velocity in sedentary women.
    Keywords:  Cardiometabolic Health; Exercise Snacks; Mitochondrial Dynamics; Muscle Oxygenation; Peripheral Blood Mononuclear Cells
    DOI:  https://doi.org/10.1152/japplphysiol.00267.2026
  46. Biochem Pharmacol. 2026 Jul 24. pii: S0006-2952(26)00626-X. [Epub ahead of print] 118287
    Mitochondria-targeted reactive species scavenger JP4-039 protects against disturbances of redox homeostasis, mitochondrial quality control, and glucose metabolism in brains of glutaryl-CoA dehydrogenase-deficient mice: A potential new therapeutic strategy for glutaric acidemia type 1.
    Renata de Britto, Leonardo de Moura Alvorcem, Manuela Bianchin Marcuzzo, Rafael T Ribeiro, Carolina Soares, Adriana Fernanda K Vizuete, Larissa D Bobermin, Gianina Teribele Venturin, Samuel Greggio, Eduardo R Zimmer, André Quincozes-Santos, Diogo Onofre de Souza, Carlos-Alberto Gonçalves, Peter Wipf, Jerry Vockley, Bianca Seminotti, Moacir Wajner, Guilhian Leipnitz.
      Glutaric aciduria type 1 (GA1) is a cerebral organic aciduria caused by deficient activity of glutaryl-CoA dehydrogenase (GCDH). Patients present with acute striatal degeneration and develop progressive cortical leukodystrophy whose pathophysiology is only partially known. As treatment for GA1 is limited, we evaluated the impact of JP4-039, a mitochondria-targeted reactive oxygen species (ROS) and electron scavenger, on redox homeostasis, mitochondrial quality control, and glucose metabolism in the cortical and striatal brain tissues of GCDH-deficient (Gcdh-/-) mice. Both tissues exhibited increases in lipid peroxidation, ROS levels, and the activities of superoxide dismutase, catalase, and glutathione S-transferase. Furthermore, glutathione reductase activity was increased, and glutathione peroxidase was reduced in the striatum, while Nrf2 mRNA levels were elevated in the cortex. Notably, most of these altered endpoints of redox homeostasis were prevented by treatment with JP4-039. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression was reduced in the cortex of Gcdh-/- mice, whereas voltage-dependent anion channel (VDAC) and dynamin-related protein 1 (DRP1) expression were increased in the striatum, signaling a disturbance of mitochondrial quality control. JP4-039 mitigated the DRP1 change. The cerebral cortex displayed reduced glucose metabolism, increased lactate levels, and elevated activities of hexokinase, pyruvate kinase, and lactate dehydrogenase (LDH), which JP4-039 mitigated. GLUT3 expression was reduced in the cerebral cortex, but JP4-039 did not change this effect. Our data suggest that redox imbalance and dysregulated mitochondrial quality control and of the glycolytic pathway contribute to the pathophysiology of GA1, and that JP4-039 may offer therapeutic benefit.
    Keywords:  Cerebral cortex; Gcdh(-/-) mice; Glucose metabolism; Glutaric aciduria type 1; JP4-039; Mitochondrial quality control; Oxidative stress; Striatum
    DOI:  https://doi.org/10.1016/j.bcp.2026.118287
  47. Aquat Toxicol. 2026 Jul 16. pii: S0166-445X(26)00232-8. [Epub ahead of print]299 107936
    α-Ketoglutarate attenuates ammonium chloride-induced ferroptosis by maintaining mitochondrial homeostasis in grass carp (Ctenopharyngodon idellus) hepatocytes.
    Yuling Zhang, Chengchen Jiang, Dapeng Li, Rong Tang.
      Ammonia nitrogen is a common pollutant in aquaculture water, which can induce oxidative stress and inhibit growth in fish. α-ketoglutarate (AKG) has been proven to play an important role in alleviating oxidative stress and maintaining mitochondrial homeostasis. To investigate the regulatory mechanism of α-ketoglutarate in ammonium chloride-induced hepatocyte ferroptosis, flow cytometry and Western blotting were performed with grass carp hepatocytes as the experimental model. The results showed that ammonium chloride exposure could significantly reduce the viability of grass carp L8824 hepatocytes, significantly increase the expression levels of lipid reactive oxygen species (LipROS) and ACSL4 protein, and simultaneously cause damage to the morphological structure and physiological function of mitochondria, thereby inducing lipid peroxidation. In addition, ammonium chloride could also disrupt the cellular iron ion transport system, leading to abnormal accumulation of intracellular iron ions and ultimately inducing hepatocyte ferroptosis. After AKG intervention, hepatocyte viability was significantly improved, the expression levels of LipROS was significantly decreased, and lipid peroxidation damage was effectively alleviated. Meanwhile, mitochondrial homeostasis was maintained but the expression levels of ferroptosis-related genes did not show a significant changes. In summary, AKG may alleviate ammonium chloride stress-mediated ferroptosis in grass carp L8824 hepatocytes by scavenging intracellular reactive oxygen species and repairing mitochondrial function. The results of this study provide a new idea for ammonia nitrogen pollution control and healthy fish culture in aquaculture.
    Keywords:  Ammonium chloride; Ferroptosis; L8824; α-Ketoglutarate
    DOI:  https://doi.org/10.1016/j.aquatox.2026.107936
  48. Comp Biochem Physiol C Toxicol Pharmacol. 2026 Jul 21. pii: S1532-0456(26)00185-7. [Epub ahead of print] 110627
    The SIRT gene family protects against oxidative stress and mitochondrial dynamic dysfunction induced by polystyrene nanoplastics in the ovaries of zebrafish (Danio rerio).
    Jiabao Peng, Wenqi Shi, Zhigang Yang, Aqin Chen.
      Micro- and nanoplastics (MNPs) are increasingly recognized as reproductive toxicants in aquatic organisms. Although numerous in vivo and in vitro studies have documented MNPs-induced reproductive damage, the underlying molecular mechanisms remain poorly understood. The SIRT protein family, a group of NAD+-dependent histone deacetylases, plays important roles in regulation of reproductive function. This study aims to systematically elucidate the role of the SIRT proteins in mediating responses to polystyrene nanoplastics (PS-NPs) in female zebrafish. Adult female zebrafish were exposed to a range of PS-NPs concentrations. Exposure resulted in a dose-dependent reduction in the gonadosomatic index (GSI), fecundity, spawning capacity, fertilization rate and hatching rate of offspring. Significant changes in SIRT family gene expression were also observed. Molecular docking analysis indicated that PS-NPs can bind to and potentially inhibit all SIRT isoforms. To further investigate the role of SIRT proteins, zebrafish were co-exposed to 1.5 mg/L PS-NPs with the SIRT activator resveratrol (RSV) or the SIRT inhibitor nicotinamide (NAM). RSV significantly upregulated ovarian SIRTs expression, attenuated PS-NPs-induced increase in reactive oxygen species, and loss of mitochondrial membrane potential in ovarian follicles. In contrast, NAM suppressed SIRTs expression and exacerbated these mitochondrial and oxidative defects. qPCR revealed that RSV increased transcription of antioxidant genes (NRF, SOD, CAT, GPX) and mitochondrial fusion/biogenesis genes (OPA1, MFN1/2, TFAM), while decreasing the fission gene (DRP1), whereas NAM produced the opposite effects pattern. Together, these results implicate SIRT proteins in protecting ovarian function against PS-NPs toxicity and suggest SIRT modulation as a potential mechanism underlying MNP-induced female reproductive dysfunction.
    Keywords:  Mitochondrial dynamics; Oxidative stress; Polystyrene nanoplastics; SIRT gene family; Zebrafish
    DOI:  https://doi.org/10.1016/j.cbpc.2026.110627
  49. Reprod Sci. 2026 Jul 20.
    Bioinformatics, Machine Learning and Functional Validation Reveal Mitophagy-Related FABP5 and HMOX1 as Diagnostic and Therapeutic Targets in Polycystic Ovary Syndrome.
    Aiqin Lian, Yuxin Li, Weijun He, Xinjian Luo, Long Jin, Chaohui Li.
      Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder characterized by ovulatory dysfunction, hyperandrogenism, and insulin resistance, in which mitochondrial dysfunction has been increasingly implicated. Mitochondria regulate energy metabolism and oxidative stress, with mitophagy maintaining cellular balance. Dysregulated mitophagy relates to PCOS metabolic issues like obesity and inflammation. This study analyzed gene expression datasets to find autophagy-related genes in PCOS, identifying AMFR, FABP5, and HMOX1 as key genes. We built a diagnostic model and confirmed their elevated expression in a hyperandrogenism-induced PCOS cell model, revealing potential small-molecule drugs targeting these genes. Our integrative bioinformatics analysis and systematic molecular experiments suggest that FABP5 and HMOX1 are potential PCOS diagnostic targets, with high-affinity compounds as therapies,highlighting the pathological relevance of mitophagy-related genes in PCOS.
    Keywords:  Dysregulated mitophagy; Integrative bioinformatics analysis; Machine learning; Molecular docking; PCOS
    DOI:  https://doi.org/10.1007/s43032-026-02156-x
  50. Biochem Pharmacol. 2026 Jul 20. pii: S0006-2952(26)00616-7. [Epub ahead of print] 118277
    Mitochondrial fission-mediated podocyte dysfunction via CaMKII/Drp1 signaling pathways contributes to lenvatinib-induced renal injury.
    Shuanghui Lu, Yueping Qiu, Yujia Chen, Luexiang Yuan, Jing Chen, Libin Pan, Junfeng Zhu, Wenxiu Xin, Haiyin Ding, Mengfei Dai, Huidi Jiang, Luo Fang.
      The adverse effects of VEGF signaling pathway inhibitors, notably renal injury manifested as proteinuria, critically impair clinical outcomes and health-related quality of life, with lenvatinib inducing the highest incidence. This study aims to investigate the mechanism of lenvatinib-induced renal injury, and then to explore potential therapeutic strategies. We identified that lenvatinib induced severe glomerular injury, characterized by proteinuria, focal segmental glomerulosclerosis, and loss of podocytes in a dose-dependent manner, but no apparent tubular injury in the mouse kidney. Further studies revealed that lenvatinib-induced glomerular injury was associated with the epithelial-mesenchymal transition-like changes of podocytes, driven by increased mitochondrial fission through CaMKⅡ-mediated upregulation of Drp1 phosphorylation at Ser616. Using zebrafish as an in vivo screening platform, we further identified several mitochondrial fission inhibitors-including metformin, andrographolide, melatonin, berberine, and mdivi-1-that exhibited protective effects against lenvatinib-induced renal edema, with metformin and melatonin showing the most pronounced efficacy. Metformin, an antidiabetic drug, was further demonstrated to alleviate lenvatinib-induced nephrotoxicity both in vitro and in vivo by reversing the epithelial-mesenchymal transition-like changes of podocytes through the suppression of Drp1(Ser616) phosphorylation. These findings provide the first evidence suggesting that increased mitochondrial fission via CaMKII/Drp1 signaling pathways in podocytes contributes to lenvatinib-induced kidney injury, and identify metformin as a clinically viable treatment option for lenvatinib-induced renal injury.
    Keywords:  CaMKII/Drp1; Lenvatinib; Mitochondrial fission; Podocyte; Renal injury
    DOI:  https://doi.org/10.1016/j.bcp.2026.118277
  51. Front Immunol. 2026 ;17 1856853
    Mitochondrial dysfunction and the regulatory cell death crosstalk network in chronic obstructive pulmonary disease: from oxidative stress mechanisms to targeted therapeutic strategies.
    Hongyan Fan, Juandi Xue, Jianghua Si.
      The sustained progression of chronic obstructive pulmonary disease (COPD) may not be independently driven by a single process such as chronic inflammation, oxidative stress, or cell death, but rather originates from a cross-amplification network among "mitochondrial dysfunction-oxidative stress-regulated cell death." In the context of mitochondrial damage, excessive generation of reactive oxygen species (ROS), damage and release of mitochondrial DNA (mtDNA), and dysregulation of mitochondrial quality control (MQC) collectively promote airway epithelial injury, sustained inflammation, alveolar destruction, and tissue remodeling. Furthermore, regulated cell death modalities such as apoptosis, necroptosis, pyroptosis, and ferroptosis are not isolated from each other but are coupled under a shared context of mitochondrial stress, exhibiting different dominant patterns across various cell types and disease stages. Adopting an integrated perspective encompassing mitochondrial dysfunction, amplified oxidative stress, and the regulated cell death (RCD) cross-network, this article synthesizes current research regarding COPD-related mechanisms, with a focus on mitochondrial damage markers, RCD activity indicators, mechanism-oriented patient stratification, and potential therapeutic strategies targeting mitochondrial homeostasis and cell death pathways. This framework facilitates the transition of COPD understanding from the traditional chronic inflammation model to a more stratified and translationally promising mitochondrial-cell death network model.
    Keywords:  chronic obstructive pulmonary disease (COPD); mitochondrial dysfunction; mitochondrial quality control; oxidative stress; pyroptosis; regulated cell death (RCD)
    DOI:  https://doi.org/10.3389/fimmu.2026.1856853
  52. Adv Sci (Weinh). 2026 Jul 20. e76686
    Gut Microbial Release of Ferulic Acid From Germinated Quinoa Alleviates Obesity-Associated Cognitive Impairment by Activating Hippocampal Mitophagy Associated with PINK1/Parkin Pathway.
    Yongli Lan, Wengang Zhang, Lei Wang, Shiyang Zhao, Yujie Song, Xinze Wang, Yutang Wang, Xijuan Yang, Shaobo Ma, Junlin Ge, Rui Guo, Xuebo Liu.
      Obesity is a major risk factor for cognitive impairment and related neurodegenerative disorders. Whole grains are rich in polyphenols and dietary fiber, with intake associated with improvements in obesity and cognitive deficits. Gut microbial genes encode enzymes that metabolize dietary polyphenols, thereby influencing host metabolic and neurological health; however, the specific functional microbes and enzymes involved remain largely unknown. Here, we demonstrate that germinated quinoa (GQF), a polyphenol-enriched whole-grain intervention, alleviates high-fat diet-induced cognitive impairment and restores gut microbial diversity more effectively than native quinoa (QF). These benefits correlate with enriched Roseburia abundance and enhanced carbohydrate-active enzyme (CAZyme) gene profiles, particularly genes encoding feruloyl esterase (FAE). GQF exerts neuroprotective effects via a microbiota-substrate co-dependent pattern, rather than simply relying on gut microbiota alone. Specifically, GQF selectively promotes FAE-harboring Roseburia hominis and R. intestinalis proliferation, thereby facilitating the release of bound ferulic acid (FA) from GQF. Liberated FA promotes neuronal growth and synaptic plasticity by activating PINK1/Parkin-dependent hippocampal mitophagy. These results underscore the indispensable role of specific gut microbes in unlocking the nutritional efficacy of GQF. In conclusion, dietary GQF and its microbe-releasable FA represent a natural nutritional strategy, providing a promising preventive and adjuvant approach for metabolic-related cognitive dysfunction.
    Keywords:   Roseburia ; ferulic acid; germinated quinoa; gut microbiota; mitophagy; synaptic plasticity
    DOI:  https://doi.org/10.1002/advs.76686
  53. Trends Biotechnol. 2026 Jul 21. pii: S0167-7799(26)00286-6. [Epub ahead of print]
    Mitochondrial engineering strategies in yeast cell factories.
    Shuo Yang, Cong Gao, Guipeng Hu, Xiaomin Li, Liming Liu.
      Yeast is widely used as a microbial chassis for sustainable chemical production, with subcellular organelles helping to organize and regulate biosynthesis. Among these organelles, mitochondria play pivotal roles in yeast cell factories by supplying metabolic resources, maintaining cellular vitality, and providing a favorable biosynthetic microenvironment. Accordingly, this review summarizes mitochondria-centered strategies for improving yeast-based chemical production. These strategies include (i) rewiring mitochondrial metabolic pathways to regulate metabolic resource supply; (ii) maintaining mitochondrial homeostasis to improve cellular vitality; and (iii) optimizing mitochondrial compartmentalization. Current bottlenecks and future opportunities are discussed, providing a framework for optimizing chemical biosynthesis in yeast cell factories.
    Keywords:  chemical biosynthesis; mitochondrial compartmentalization; mitochondrial homeostasis; mitochondrial metabolic rewiring; yeast cell factory
    DOI:  https://doi.org/10.1016/j.tibtech.2026.07.007
  54. Adv Sci (Weinh). 2026 Jul 23. e76778
    A Blood-Derived Factor Rescues ALS: Platelet Factor 4 Activates OPTN-Dependent Autophagy to Clear SOD1 Aggregates Independently of PINK1.
    Qingjian Xie, Yanbo Zhu, Wenhua Jiang, Haobo Xie, Yaojia Li, Mengjie Hu, Kezheng Li, Huan Yu, Yixuan Pan, Chaoyi Jiang, Xueqin Song, Dongsheng Fan, Binbin Deng.
      Peripheral factors that systemically regulate amyotrophic lateral sclerosis (ALS) have remained elusive-until now. Here, by integrating population-scale epidemiology with mechanistic dissection, we identify platelet factor 4 (PF4) as the central driver of a circulating neuroprotective axis that restores proteostasis and rescues ALS. In a prospective cohort of >500 000 UK Biobank participants, platelet indices were strongly associated with ALS risk, and serum PF4 levels were significantly reduced in ALS patients. Systemic administration of recombinant PF4 in hSOD1G93A mice produced dramatic therapeutic effects: extended survival, preserved motor function, attenuated neuroinflammation, and reduced neuromuscular junction denervation. Remarkably, this efficacy appears pathology-selective-robust in SOD1-driven models but shows no observable effect in TDP-43 or C9orf72 ALS models. Mechanistically, PF4 achieves what few molecules can: it engages the cell surface receptor LRP1 to activate the TBK1-OPTN signaling axis, restoring impaired autophagic flux through a PINK1/Parkin-independent pathway requiring ATG7, establishing a previously unrecognized peripheral platelet-autophagy-neuron axis that facilitates the co-clearance of pathological SOD1 aggregates and damaged mitochondria. This study unveils PF4 as a first-in-class circulating autophagy regulator with therapeutic potential in ALS. Beyond identifying a candidate biomarker and drug lead, it reveals that systemic factors can directly engage central proteostatic machinery-opening a new frontier for ALS therapy.
    Keywords:  OPTN; PF4; SOD1; amyotrophic lateral sclerosis; mitophagy; proteostasis
    DOI:  https://doi.org/10.1002/advs.76778
  55. iScience. 2026 Aug 21. 29(8): 116822
    Retraction notice to "CircTMEM165 facilitates endothelial repair by modulating mitochondrial fission via miR-192/SCP2 in vitro and in vivo" [iScience 27 (2024) 109502].
    Yan Liu, Yanyan Yang, Min Li, Xiuxiu Fu, Xiangqin He, Xiaoxin Li, Jae Youl Cho, Pei-Feng Li, Tao Yu.
      [This retracts the article DOI: 10.1016/j.isci.2024.109502.].
    DOI:  https://doi.org/10.1016/j.isci.2026.116822
  56. Bioact Mater. 2026 Dec;66 412-427
    Mitochondria-targeted MXene-based nanozymes promote mitophagy and inhibit mtDNA-triggered cGAS/STING inflammation in osteoarthritis.
    Tiancheng Li, Ao Zheng, Cheng Zhu, Yixin Li, Zitong Yang, Xinyue Tang, Yu Jin, Ting Dong, Bin Li, Lunguo Xia, Lingyan Cao, Bing Fang.
      Osteoarthritis (OA) is a prevalent and debilitating joint disease driven by progressive cartilage degradation, mitochondrial dysfunction, and chronic inflammation. In this study, we introduced MS@PMXene-TK, an innovative, mitochondria-targeted nanozyme designed for cartilage repair by addressing these key pathological features. This nanozyme platform uniquely integrated a chondro-inductive peptide (SPPEPS)-loaded, polydopamine (PDA)-modified MXene core (S@PMXene) with a reactive oxygen species (ROS)-responsive thioketal-linked polyethylene glycol (PEG-TK) shell and a mitochondria-targeting peptide (MTP-131), enabling precise and responsive therapeutic intervention at the subcellular level. In vitro and in vivo analyses demonstrated that MS@PMXene-TK effectively scavenged mitochondrial ROS within chondrocytes, acting as a "cruise missile," which led to restoration of mitochondrial membrane potential and promotion of mitophagy. This cascade mitigated mtDNA leakage and subsequent activation of the cGAS/STING pathway, a critical inflammatory driver in OA. Concurrently, sustained release of SPPEPS enhanced chondrogenic marker expression and extracellular matrix synthesis, while alleviating macrophage-mediated inflammatory responses, further modulating the inflammatory microenvironment. In an anterior cruciate ligament transection (ACLT)-induced OA mouse model, intra-articular administration of MS@PMXene-TK significantly improved cartilage protection and subchondral bone integrity. These findings establish the potential of this targeted, multi-modal nanozyme strategy to disrupt intertwined pathologies of oxidative stress and inflammation in OA, offering a promising avenue for OA treatment.
    Keywords:  Mitochondrial DNA; Mitophagy; Nanozymes; Osteoarthritis; cGAS/STING
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.07.010
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