bims-ripira 2026-03-01 papers

bims-ripira

Biomed News

on RRM2B MDMD in Adults

Issue of 2026–03–01
seventeen papers selected by
Martín Lopo

The Synergy Between Mitochondrial Function and Innate Heat in Traditional Persian Medicine: A Modern Scientific Perspective on Thermoregulation.
4,5-dihydroxyhexanoic acid is a robust circulating and urine marker of mitochondrial disease and its severity.
Translational studies of chronic supplementation with a mitochondria-targeted antioxidant to improve physical function with ageing.
PRMT5 in mitochondria regulates mtDNA stability through TFAM arginine methylation.
Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions.
Repeated Disuse Atrophy Imprints a Molecular Memory in Skeletal Muscle: Transcriptional Resilience in Young Adults and Susceptibility in Aged Muscle.
Beyond Decellularization: Remnant Mitochondrial DNA Can Act as Hidden Damage-Associated Molecular Pattern.
Magnetic resonance spectroscopy as a non-invasive tool for assessing brain and muscle adaptation to exercise training in older age: a scoping review into existing research.
Linking mitochondrial DNA release to neurodegeneration and cognitive decline.
Changes in apolipoproteins following ingestion of a beverage delivering β-hydroxybutyrate: results from a randomized placebo-controlled trial.
Mitochondrial function-related genes and ionizing radiation-induced intestinal injury: mechanisms and research progress.
Metabolic Perturbation Exacerbates Sinoatrial Node Dysfunction in Heart Failure.
Mitochondrial abnormalities in idiopathic inflammatory myopathies.
Profiling mitochondrial DNA indices across whole blood, plasma, and CSF in amyotrophic lateral sclerosis.
Mitochondria at the Crossroads of Cardiovascular Disease: Mechanistic Drivers and Emerging Therapeutic Strategies.
Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?
Mitochondria transfer in Glioblastoma.

Avicenna J Med Biotechnol. 2025 Oct-Dec;17(4):17(4): 234-241

The Synergy Between Mitochondrial Function and Innate Heat in Traditional Persian Medicine: A Modern Scientific Perspective on Thermoregulation.

Majid Nimrouzi, Masoud Hashemzaei.

  This study investigates the synergy between Traditional Persian Medicine (TPM)'s concept of innate heat (Hararat-e-Gharizi) and modern mitochondrial thermoregulation. TPM emphasizes innate heat as essential for sustaining life, paralleling modern understandings of mitochondrial ATP production and heat generation. This integration occurs through mitochondrial biogenesis, proton leak (via uncoupling proteins), and Reactive Oxygen Species (ROS) signaling, which correspond to the TPM concept of heat sustaining vital functions. These findings may guide novel therapeutic strategies that integrate TPM principles with mitochondrial biology. A comprehensive review of historical TPM texts and modern literature was conducted, comparing innate heat with mitochondrial roles in thermoregulation and energy balance. Data from PubMed, Google Scholar, and Scopus were analyzed to explore mechanisms of heat production in both traditional and modern contexts. Findings demonstrated that TPM's innate heat correlates with mitochondrial biogenesis, heat generation via Uncoupling Proteins (UCP1), and ROS regulation. These concepts reflect TPM's understanding of maintaining bodily warmth for health and longevity. The relationship between Hararat-e-Gharizi and mitochondrial thermogenesis offers a bridge between ancient medicinal practices and modern cellular biology. Both emphasize the role of heat in maintaining homeostasis and preventing disease, with modern science validating TPM's holistic approach. Clarifying these mechanisms provides deeper insight into therapeutic implications, highlighting thermodynamic parallels and the role of ROS signaling as a novel framework for understanding disease etiology and treatment. This study bridges Traditional Persian Medicine and modern mitochondrial thermoregulation, introducing integrative perspectives for personalized healthcare. It also highlights thermodynamic parallels and ROS signaling as a novel framework for understanding disease etiology and treatment. This study underscores the relevance of TPM's innate heat in modern medicine, emphasizing the importance of mitochondrial efficiency in thermoregulation and overall health. Integrating these perspectives can enhance personalized therapeutic strategies for disease prevention and longevity.

Keywords:  Biology; Biomedical technology; Body temperature regulation; Hot temperature; Literature; Mitochondrial uncoupling proteins

DOI:  https://doi.org/10.18502/ajmb.v17i4.20069
bioRxiv. 2026 Feb 12. pii: 2026.02.10.705117. [Epub ahead of print]

4,5-dihydroxyhexanoic acid is a robust circulating and urine marker of mitochondrial disease and its severity.

Owen S Skinner, Maria Miranda, Fangcong Dong, Tessa Struhl, Melissa A Walker, Grigorij Schleifer, Matthew T Henke, Jon Clardy, Michio Hirano, Darryl C De Vivo, Eric A Schon, Kristin Engelstad, Stephanie E Siegmund, Catherine Laprise, Christine Des Rosiers, Vamsi K Mootha, Rohit Sharma.

Management of patients with mitochondrial respiratory chain diseases is challenging, in part because of our incomplete understanding of pathogenesis and a lack of biomarkers. Unknown metabolites account for >90% of detected features in modern metabolomics experiments and hold immense untapped promise for new basic and biomedical research. We recently used mass spectrometry-based metabolomics to identify and validate 19 circulating blood-based biomarkers for patients with the mitochondrial DNA (mtDNA) m.3243A>G pathogenic variant, which is the most frequent cause of the mitochondrial disorder MELAS ( m itochondrial e ncephalomyopathy, lactic a cidosis, and s troke-like episodes). However, the most significantly changing biomarker corresponded to an "unknown" metabolite. Here, we combine cheminformatics with analytical chemistry and identify that feature as 4,5-dihydroxyhexanoic acid (4,5-DHHA), a metabolite previously associated with inherited defects of gamma-aminobutyric acid (GABA) catabolism, but with no prior links to mitochondrial respiratory chain disorders. We validate this finding in an independent MELAS cohort and further show that 4,5-DHHA levels correlate with disease severity and are elevated in patients with other forms of mitochondrial disease and sepsis. Furthermore, brain 4,5-DHHA levels were elevated in two genetic mouse models of mitochondrial disease. In vitro and tissue culture experiments indicate that 4,5-DHHA is generated when the GABA catabolite succinic semialdehyde reacts with an intermediate of the pyruvate dehydrogenase reaction and is sensitive to mitochondrial complex I function. Our work identifies 4,5-DHHA as a robust plasma and urine marker of mitochondrial dysfunction in humans and reveals new connections between the respiratory chain and GABA metabolism.
Significance Statement: Inborn errors of the mitochondrial respiratory chain cause severe, progressive diseases, yet effective treatments and biomarkers remain limited. Modern metabolomics detects thousands of molecules in biofluids, but the vast majority are unidentified. In this study, we investigate the most significantly altered blood metabolite in patients with the most common mitochondrial disease - MELAS ( m itochondrial e ncephalomyopathy, lactic a cidosis, and s troke-like episodes) - and identify it as an 4,5-dihydroxyhexanoic acid (4,5-DHHA). We show that 4,5-DHHA is reproducibly elevated and correlates with severity. Levels are increased across multiple mitochondrial disorders as well as in sepsis and rise when respiratory chain function is impaired. These findings establish 4,5-DHHA as a promising biomarker of mitochondrial dysfunction and reveal a link to dysregulated GABA metabolism.

DOI: https://doi.org/10.64898/2026.02.10.705117
J Physiol. 2026 Feb 24.

Translational studies of chronic supplementation with a mitochondria-targeted antioxidant to improve physical function with ageing.

Kevin O Murray, Rachel A Gioscia-Ryan, Jaime N Justice, Jessica R Santos-Parker, Nina Z Bispham, David A Hutton, Sanna Darvish, Jill Miyamoto-Ditmon, Zachary S Clayton, Michel Chonchol, Douglas R Seals, Matthew J Rossman.

  Declines in physical function with advancing age increase the risk of functional limitations and chronic disease. Excess mitochondrial reactive oxygen species (mitoROS)-related oxidative stress is linked to physical dysfunction with ageing, but the effects of therapies targeting excess mitoROS on age-associated physical dysfunction are unclear. Here, we determined the efficacy of the mitochondria-targeted antioxidant MitoQ for improving multiple domains of physical function, first in old mice and then in high-functioning older adults in a randomized, placebo-controlled, cross-over design clinical trial. In old male C57BL6/N mice (N = 22-26; 27 months), we found that 4 weeks of treatment with MitoQ (250 µm in the drinking water) attenuated the age-related decline in grip strength, co-ordination, and endurance without effects in young mice (N = 18-20; 6 months). The effects of MitoQ in old mice were accompanied by lower levels of skeletal muscle mitochondria-specific superoxide production and markers of mitoROS-related oxidative stress (i.e. phosphorylated SHC adaptor protein 1, isoform p66) and inflammation (i.e. interleukin-6, tumour necrosis factor-alpha, interferon-gamma). In the clinical trial, we did not observe convincing effects of 6 weeks of MitoQ (20 mg day-1) treatment on physical function in healthy older adults (N = 18; aged 60-79 years). However, exploratory subgroup analyses suggest possible effects of MitoQ on peak leg extension power and grip strength in participants ≥70 years of age. Our findings provide preclinical, proof-of-concept evidence for targeting excess mitoROS with MitoQ to reverse physical dysfunction with ageing. Although the effects of MitoQ did not directly translate to high functioning older adults, our initial observations suggest MitoQ may have greater efficacy in older, more physically frail individuals. KEY POINTS: Excess mitochondrial reactive oxygen species (mitoROS)-related oxidative stress is linked to physical dysfunction with ageing, but the effects of therapies targeting excess mitoROS on age-associated physical dysfunction are unclear. In old mice, chronic supplementation with the mitochondria-targeted antioxidant MitoQ improves measures of physical function, which was accompanied by reductions in mitochondria-specific superoxide production in skeletal muscle. The effects of MitoQ in old mice did not directly translate to humans as there were no convincing effects on measures of motor function in a randomized, placebo-controlled, cross-over design clinical trial of 6 weeks of 20 mg day-1 MitoQ. However, in participants ≥70 years of age, we observed possible evidence of efficacy of MitoQ supplementation for improving select measures of strength. Future clinical trials with MitoQ and possibly other mitochondria-targeted antioxidant approaches for enhancing physical function with ageing should focus on older adults of more advanced age or more frail clinical populations.

Keywords:  MitoQ; inflammation; motor function; older adults; postmenopausal women; reactive oxygen species; skeletal muscle; superoxide

DOI:  https://doi.org/10.1113/JP289428
Nat Commun. 2026 Feb 23.

PRMT5 in mitochondria regulates mtDNA stability through TFAM arginine methylation.

Sangheeta Bhattacharjee, Sayan Das, Banhi Chowdhury, Benu Brata Das.

Protein arginine methyltransferase 5 (PRMT5) catalyzes arginine methylation and regulates cellular functions such as proliferation, RNA splicing, and nuclear DNA damage response. This study uncovers that a fraction of nuclear-encoded PRMT5 localizes to the mitochondria, which is critical for maintaining mitochondrial DNA (mtDNA) homeostasis. PRMT5 knockout (PRMT5-/-) cells had reduced nucleoid counts, diminished mtDNA copy numbers, disrupted the balance of the mitochondrial fission-fusion cycle, impaired mitochondrial plasticity, and nucleoid trafficking. PRMT5-/- cells are hypersensitive to mtDNA-damaging agents, exhibit reduced mitochondrial transcripts, oxidative phosphorylation, and respiratory capacity that triggers cell death. We identify TFAM as a previously unrecognized interacting partner of PRMT5, which catalyzes symmetric dimethylation of TFAM at R82 residue, which is crucial for mtDNA binding and protection. Defective R82-methylation destabilizes TFAM, which is then degraded by LonP1. Together, we establish that PRMT5 is a mitochondrial enzyme and a key regulator of TFAM in mtDNA maintenance.

DOI: https://doi.org/10.1038/s41467-026-69676-7
Int J Mol Sci. 2026 Feb 19. pii: 1981. [Epub ahead of print]27(4):

Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions.

Eman Salem Algariri, Fazlina Nordin, Min Hwei Ng, Izyan Mohd Idris, Norwahidah Abdul Karim, Gee Jun Tye, Wan Safwani Wan Kamarul Zaman.

  Mitochondrial dysfunction is a central pathological feature of a wide range of inherited and acquired disorders and is characterized by impaired oxidative phosphorylation, disrupted cellular energy metabolism, and excessive oxidative stress. Although advances in molecular diagnostics have improved disease recognition, effective disease-modifying therapies remain limited, and clinical outcomes are often suboptimal, highlighting the need for novel therapeutic strategies. Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have emerged as promising candidates for targeting mitochondrial dysfunction due to their regenerative, immunomodulatory, and metabolic regulatory properties. In this review, we provide a comprehensive overview of recent in vitro and in vivo studies investigating the capacity of MSCs and MSC-EVs to restore mitochondrial function by enhancing mitochondrial respiration, improving cellular bioenergetics, and reducing oxidative stress across diverse disease models. We further discuss the underlying mechanisms involved, including mitochondrial transfer, delivery of functional mitochondrial components, and modulation of the cellular microenvironment. Finally, we highlight the key advantages, translational potential, and remaining challenges associated with MSC- and MSC-EV-based therapies for mitochondrial dysfunction.

Keywords:  MSC-EVs; MSC-base therapy; exosomes; mitochondrial diseases; mitochondrial transfer; oxidative phosphorylation

DOI:  https://doi.org/10.3390/ijms27041981
Adv Sci (Weinh). 2026 Feb 25. e22726

Repeated Disuse Atrophy Imprints a Molecular Memory in Skeletal Muscle: Transcriptional Resilience in Young Adults and Susceptibility in Aged Muscle.

Daniel C Turner, Truls Raastad, Max Ullrich, Stian F Christiansen, Hazel Sutherland, James Boot, Eva Wozniak, Charles Mein, Emilie Dalbram, Jonas T Treebak, Daniel J Owens, David C Hughes, Sue C Bodine, Jonathan C Jarvis, Adam P Sharples.

  Disuse-induced muscle atrophy commonly occurs following illness, injury, or falls and becomes increasingly frequent with ageing. Whether skeletal muscle retains a "memory" of repeated disuse remains unknown. We investigated repeated lower-limb immobilization in young adults and a refined aged rat model, integrating physiological, multi-omic, immunohistochemical, biochemical, and primary human muscle stem cell (MuSC) analyses. To enable robust age comparisons, we integrated previously published young rat data with newly generated aged rat data. In young human muscle, repeated disuse elicited attenuated transcriptional perturbations in oxidative and mitochondrial pathways, suggestive of a protective molecular memory, despite similar atrophy to initial disuse. In contrast, aged muscle exhibited a detrimental memory, characterized by greater atrophy, exaggerated suppression of aerobic metabolism genes despite recovery after initial disuse, NAD+ and mitochondrial DNA depletion, and activation of proteasomal, extracellular-matrix, and DNA-damage pathways. Whereas young rats recovered muscle mass after initial disuse, aged rats failed to do so. Across species, repeated disuse induced DNA hypermethylation and downregulation of aerobic metabolism and mitochondrial gene networks. NR4A1 and NR4A3 were among the strongest disuse-suppressed genes; NR4A1 acquired recovery-phase hypermethylation that maintained its transcriptional repression, while NR4A3 was the most downregulated gene after initial atrophy and remained persistently suppressed into recovery. Acetylcholine receptor subunit genes (CHRNA1, CHRND) were epigenetically primed, demonstrating hypomethylation and strong upregulation after disuse, and further amplification after repeated atrophy, while CHRNG was selectively induced after repeated atrophy only. NMRK2, an NAD+ biosynthesis gene, was the most downregulated gene across both atrophy periods, and supplementation with its substrate, nicotinamide riboside (NR), improved myotube size in MuSCs derived post-atrophy. Overall, repeated disuse atrophy imprints a molecular memory in skeletal muscle shaping transcriptional resilience in young adults and exaggerated susceptibility in aged muscle.

Keywords:  AChR (CHRNA1, CHRND, CHRNG); DNA methylation; NAD+ metabolism; NMRK2; NR4A1; NR4A3 ; aerobic metabolism; aging; disuse atrophy; mtDNA; muscle memory; muscle stem cells; nicotinamide riboside; skeletal muscle; transcriptome

DOI:  https://doi.org/10.1002/advs.202522726
Bioengineering (Basel). 2026 Feb 09. pii: 193. [Epub ahead of print]13(2):

Beyond Decellularization: Remnant Mitochondrial DNA Can Act as Hidden Damage-Associated Molecular Pattern.

Elena V A van Hengel, Kuan Liu, Henk P Roest, Jorke Willemse, Kimberley Ober-Vliegen, Selina M W Teurlings, Jeroen de Jonge, Monique M A Verstegen, Luc J W van der Laan.

  Tissue decellularization aims to obtain bioscaffolds for regenerative applications by removing all cellular components while preserving the extracellular matrix (ECM) architecture. Although decellularization removes the majority of linear nuclear DNA (nDNA), residual amounts remain detectable. However, the fate of circular mitochondrial DNA (mtDNA) after decellularization has not yet been reported. Cell death or injury can cause the release of mtDNA, which is resistant to breakdown by exonucleases. Extracellular mtDNA acts as a damage-associated molecular pattern (DAMP) that can trigger immune responses. The aim of this study is to assess the presence of residual mtDNA in the liver, bile duct, and vascular scaffolds after decellularization and whether this causes inflammatory responses in macrophages. Decellularized tissues showed a marked reduction in total DNA content well below the threshold of 50 ng/mg tissue. However, in liver and vascular scaffolds, a relative increase in the mtDNA:nDNA ratio was detected in the remnant DNA fraction. Residual mtDNA in bioscaffolds acted as DAMPs causing macrophage activation, as shown by increased cell proliferation and cytokine production. Strategies to further reduce remnant mtDNA were tested. We found that treatment with the endonuclease enzyme HpaII was effective in degrading residual mtDNA. Importantly, mtDNA removal resulted in a significantly reduced macrophage activation. In conclusion, our study shows that mtDNA is relatively resistant to the decellularization procedure and can act as a DAMP in bioscaffolds. This underscores the importance of removing mtDNA from decellularized bioscaffolds to improve the immunocompatibility for biomedical applications.

Keywords:  damage-associated molecular pattern (DAMP); decellularization; extracellular matrix (ECM); innate immune response; macrophages; mitochondrial DNA; nuclear DNA; restriction enzyme digestion; tissue engineering

DOI:  https://doi.org/10.3390/bioengineering13020193
Exp Gerontol. 2026 Feb 24. pii: S0531-5565(26)00060-4. [Epub ahead of print] 113082

Magnetic resonance spectroscopy as a non-invasive tool for assessing brain and muscle adaptation to exercise training in older age: a scoping review into existing research.

Oron Levin, Ivica Just, Radka Klepochova, Shannon Helsper, Wouter Vints, Ana Filipa Silva, Antoine Langeard, Salit Bar Shalom, Christina Karatzaferi, Maryam Ziaei, Michel Audiffren, Claudia Voelcker-Rehage, Yael Netz, Nerijus Masiulis, Uwe Himmelreich, Martin Krššák.

   BACKGROUND: Exercise training has attracted increasing attention as a non-pharmacological intervention approach to counteract age-related deterioration of brain and muscle function, yet objective biomarkers are needed to understand mechanisms and optimize interventions. Magnetic resonance spectroscopy (MRS) provides non-invasive, in vivo assessment of metabolic profiles altered by aging and exercise. However, MRS-based exercise research in older populations remains limited. This scoping review aims to identify brain and muscle metabolites detectable by MRS that can serve as markers of exercise training effects in aging.
METHODS: We conducted a literature search from inception to October 2024 in PubMed, Embase, Web of Science, and Scopus. Inclusion criteria comprised randomized control trials (RCT) and observational studies including older adults (≥60 years) who underwent exercise training interventions which were preceded/followed by brain/muscle MRS scanning.
RESULTS: Fourteen studies were included. Exercise intervention characteristics varied from low or moderate aerobic type of exercise to high intensity training, with the interventions placing variable emphasis on the strength-endurance continuum. Scanning methods were 1H brain MRS (n = 6), 31P brain MRS (n = 1), 31P muscle MRS (n = 8) and 1H muscle MRS (n = 1). Main 1H-MRS brain neurometabolic outcomes were the ratios to creatine of total N-acetyl-aspartate (tNAA/tCr) and total choline (tCho/tCr) in the right/left hippocampus. However, findings regarding the effect of exercise training interventions on these neurometabolic outcomes were inconclusive. 31P muscle MRS demonstrated an increase in phosphocreatine (PCr) recovery rate from pre-to-post exercise suggesting an improvement of mitochondrial function following exercise when applying exercise interventions with an emphasis on improving cardiometabolic functions.
CONCLUSIONS: Despite limited guidance on methods and biomarkers, this scoping review supports MRS as a promising tool for monitoring exercise-induced metabolic changes in muscle and brain of older adults. However, standardized methodologies and larger number of studies are required to determine which metabolites reliably reflect exercise benefits in aging brain and muscle.

Keywords:  Brain neuroplasticity; Energy metabolites; Exercise training; Mitochondrial function; Neuroinflammation; Neurometabolites; Neuronal density

DOI:  https://doi.org/10.1016/j.exger.2026.113082
Ageing Res Rev. 2026 Feb 21. pii: S1568-1637(26)00054-1. [Epub ahead of print]117 103062

Linking mitochondrial DNA release to neurodegeneration and cognitive decline.

Zongwei Fang, Catarina Barbosa, Daniela Marinho, Rita Peixoto, Ildete Luísa Ferreira, João Laranjinha, A Cristina Rego.

  Mitochondrial DNA (mtDNA) has been recognized as a key link between mitochondrial dysfunction and neuroinflammation in neurodegenerative diseases. Beyond being a vulnerable target of oxidative damage, mtDNA can act as a damage-associated molecular pattern when released from mitochondria, triggering innate immune signaling pathways in the nervous system. This review synthesizes current evidence on the mechanisms regulating mtDNA escape from mitochondria into the cytosol and its subsequent intracellular and extracellular effects, reframing mtDNA as an active driver of inflammatory processes rather than a passive by-product of mitochondrial injury. We discuss how defects in mitochondrial quality control, particularly impaired mitophagy and macroautophagy, promote the accumulation of damaged mtDNA, including its release via mitochondria-derived vesicles, exosomes or as cell-free mtDNA. By integrating mitochondrial dysfunction, immune activation, and clearance pathways, this review highlights the mitochondria-immune axis as a central contributor to neurodegeneration and cognitive decline, identifying upstream molecular targets with potential for therapeutic intervention.

Keywords:  Damage-associated molecular patterns (DAMPs); Inflammation; Mitochondrial dysfunction; Mitophagy; Neurodegeneration; Neurodegenerative diseases; Reactive oxygen species (ROS)

DOI:  https://doi.org/10.1016/j.arr.2026.103062
Front Nutr. 2025 ;12 1726174

Changes in apolipoproteins following ingestion of a beverage delivering β-hydroxybutyrate: results from a randomized placebo-controlled trial.

Yutong Liu, Wandia Kimita, Sakina H Bharmal, Maxim S Petrov.

   Background: Apolipoproteins play important roles in the metabolism of triglyceride-rich lipoproteins. Ketone monoester β-hydroxybutyrate (KEβHB) has been shown to reduce the circulating levels of remnant cholesterol and triglycerides. However, the mechanisms behind this action remain unknown.
Aim: To investigate the effect of KEβHB supplementation on apolipoproteins and to study whether circulating levels of triglycerides play a role in this effect.
Methods: The study was a randomized placebo-controlled trial, registered at https://www.clinicaltrials.gov/ (NCT03889210). It included 18 adults (12 men and 6 women) with prediabetes (defined as per the American Diabetes Association criteria). Following an overnight fast, participants ingested a KEβHB or a placebo beverage in a cross-over manner. Serial blood samples were collected from baseline to 150 min at intervals of 30 min. The endpoints were changes in apolipoprotein (apo) A-I, apo B, apo B-48, apo C-II, apo C-III, and apo E. Area under the curve (AUC) analyses were calculated to estimate changes in the studied apolipoproteins over time. Participants were further stratified into 'hypertriglyceridemia' and normal triglyceride levels subgroups.
Results: Ingestion of the KEβHB beverage led to a significantly higher AUC for apo C-II (p = 0.023) in the overall cohort. No statistically significant differences in AUCs were found for the other studied apolipoproteins. The subgroup analysis showed significantly lower levels of apo B (and higher levels of apo C-II) after the KEβHB beverage in individuals with hypertriglyceridemia only. No significant associations were found for the other studied apolipoproteins in either subgroup.
Conclusion: Exogenously induced acute ketosis resulted in a significantly elevated apo C-II compared with the placebo. Further, the levels of apo B were significantly lowered following ingestion of the KEβHB beverage only among individuals with hypertriglyceridemia. Acute nutritional ketosis may be considered as a potential approach to reduce atherogenic triglyceride-rich lipoproteins in individuals at high cardiovascular disease risk.

Keywords:  acute nutritional ketosis; apolipoproteins; cardiovascular risk; prediabetes; triglyceride-rich lipoproteins

DOI:  https://doi.org/10.3389/fnut.2025.1726174
Int J Radiat Biol. 2026 Feb 25. 1-12

Mitochondrial function-related genes and ionizing radiation-induced intestinal injury: mechanisms and research progress.

Zhongwei Zhang, Jun Liu, Qing-Jie Liu.

   PURPOSE: Ionizing radiation-induced intestinal injury (RIII) is a significant complication of radiotherapy and nuclear radiation incidents. Mitochondria, the centers of energy metabolism and apoptosis, are pivotal in the pathogenesis of RIII. Under irradiation conditions, multiple mitochondrial function-related genes modulate the production of reactive oxygen species and ATP, maintain mitochondrial DNA, induce mitophagy, and activate the apoptotic pathway associated with mitochondrial dysfunction, leading to intestinal tissue injury. Mitochondrial function-related genes are pivotal in maintaining the normal function of mitochondria and moderate RIII. This review summarizes the mechanisms of mitochondrial function-related genes in RIII and potential therapeutic strategies, aiming to provide references for further research on RIII and clinical prevention and treatment.
CONCLUSION: Mitochondrial dysfunction driven by the dysregulation of genes related to mitochondrial function (nuclear genes and mitochondrial genome) is a key mechanism of RIII pathogenesis. At present, research on pivotal regulators remains limited, necessitating deeper investigation with multi-omics approaches. Precisely targeting these mitochondrial function-related genes offers a promising therapeutic strategy for reducing mitochondrial damage and treating RIII.

Keywords:  Radiation-induced intestinal injury; apoptosis; electron transport chain; mitochondrial function-related genes; oxidative stress

DOI:  https://doi.org/10.1080/09553002.2026.2630995
bioRxiv. 2026 Feb 10. pii: 2026.02.06.704519. [Epub ahead of print]

Metabolic Perturbation Exacerbates Sinoatrial Node Dysfunction in Heart Failure.

Lu Ren, Yu Liu, Hao Zhang, Daphne A Diloretto, Yang Zheng, Arianne Caudal, Mengjie Xie, Wenshu Zeng, Ryan L Woltz, Hye Sook Shin, Richard Q Ngo, Guy A Perkins, Gabriela Grigorean, Ebenezer N Yamoah, Joseph C Wu, Nipavan Chiamvimonvat, Phung N Thai.

Heart failure (HF) affects approximately 6.2 million people in the United States, with a 5-year mortality exceeding 50%. Bradyarrhythmia, a known complication in HF due to sinoatrial node (SAN) dysfunction (SAND), increases the morbidity and mortality of HF patients. Insights into the mechanistic underpinnings of SAND in HF could therefore uncover vital therapeutic targets to improve clinical outcomes. The SAN cells are endowed with a dense mitochondrial network crucial for sustaining their pacemaking function on a beat-to-beat basis. We have previously demonstrated significant disruptions in the mitochondrial-sarcoplasmic reticulum connectomics, resulting in abnormal mitochondrial Ca 2+ handling and impaired mitochondrial function in HF. Here, we hypothesize that the metabolic perturbation is one of the critical mechanisms underlying SAND. To this end, we took advantage of a multi-omics approach combined with ultra-resolution imaging and functional analyses to decipher the metabolic shift that transpires in the HF SAN. Our findings revealed significant metabolic remodeling within the SAN mitochondria in HF, with a diminished reliance on fatty acid β-oxidation, enhanced utilization of ketone bodies, and heightened dependence on carbohydrate catabolism. Notably, metabolomics analyses identified the pronounced increase of glucosylceramides and ceramides as one of the mechanisms leading to mitochondrial dysfunction. We directly test this hypothesis and demonstrate that ceramides induce a dose-dependent metabolic shift from oxidative phosphorylation to glycolysis. Importantly, these alterations lead to a significant impairment in SAN automaticity in a dose-dependent manner. Collectively, the findings support the notion that ceramides are not only markers of metabolic derangement, but also active mediators of mitochondrial and metabolic dysfunction in the SAN. Overall, the study provides evidence that ceramides may be a potential therapeutic target for mitigating SAND in HF.

DOI: https://doi.org/10.64898/2026.02.06.704519
Clin Exp Rheumatol. 2026 Feb;44(2): 384-389

Mitochondrial abnormalities in idiopathic inflammatory myopathies.

Francesca Torri, Giulia Ricci, Michelangelo Mancuso, Gabriele Siciliano.

OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of acquired muscle disorders characterised by immune-mediated muscle damage and systemic involvement. Increasing evidence highlights mitochondrial abnormalities as a key contributor to muscle weakness, inflammation, and disease progression. This review aims to summarise current knowledge on the mechanisms, histopathological features, and clinical implications of mitochondrial dysfunction in IIMs, as well as to discuss emerging therapeutic strategies targeting mitochondrial impairment.
METHODS: A narrative review of the literature was conducted using PubMed, with no temporal restrictions. Only English-language articles were included. Search terms comprised "inflammatory myopathies," "mitochondrial abnormalities," and "mitochondrial antibodies AND inflammatory myopathies." Studies addressing mitochondrial structure and function, histopathological findings, autoantibodies targeting mitochondrial components, and therapeutic approaches in IIMs were selected and analysed.
RESULTS: Mitochondrial dysfunction in IIMs involves impaired oxidative phosphorylation, increased oxidative stress, disrupted calcium homeostasis, defective mitophagy, and mitochondrial DNA damage. Histopathological findings include cytochrome c oxidase-negative fibres, ragged red fibres, abnormal mitochondrial morphology, and altered mitochondrial distribution, particularly prominent in inclusion body myositis. Inflammatory mechanisms further exacerbate mitochondrial injury through cytokine signalling, cytotoxic immune responses, and interferon-mediated pathways. Autoantibodies targeting mitochondrial components, such as anti-NDUFA11 and anti-mitochondrial antibodies, define subgroups with more severe or refractory disease. Therapeutic strategies reducing inflammation may indirectly improve mitochondrial function, while novel approaches, including interferon blockade, mitochondrial transplantation, and exercise-based interventions, show promise in restoring bioenergetics.
CONCLUSIONS: Mitochondrial dysfunction represents a central pathogenic mechanism in IIMs, tightly interwoven with immune-mediated muscle damage. Targeting both inflammatory and mitochondrial pathways may offer more effective and personalised therapeutic strategies for patients with inflammatory myopathies.

DOI: https://doi.org/10.55563/clinexprheumatol/qctyi2
J Neurol Sci. 2026 Feb 06. pii: S0022-510X(26)00079-1. [Epub ahead of print]483 125797

Profiling mitochondrial DNA indices across whole blood, plasma, and CSF in amyotrophic lateral sclerosis.

Jiongming Bai, Xinyuan Pang, Hongfen Wang, Ying Zhang, Yahui Zhu, Jiarui Zhao, Yifan Li, Mao Li, Xusheng Huang.

   BACKGROUND: Recent studies increasingly implicate mitochondrial DNA (mtDNA) alterations in neurodegenerative diseases, but findings across studies remain inconsistent. We aimed to characterize mtDNA indices across whole blood, plasma and CSF compartments and evaluate their clinical relevance.
METHODS: We enrolled two study cohorts: (1) a whole blood cohort of 102 ALS patients; and (2) a plasma and cerebrospinal fluid (CSF) cohort including 132 ALS patients and 62 non-neurodegenerative controls. The D-loop and COX3 regions were selected as representative mtDNA fragments, while B2M was used as a nuclear reference. Quantification was performed using SYBR Green-based quantitative PCR.
RESULTS: In whole blood, higher D-loop/COX3 ratios were associated with better functional status and longer survival. In the cell-free compartments, CSF ccf-mtDNA markers (D-loop and COX3) were significantly higher in ALS than in controls, whereas plasma abundance showed no significant group difference. Within ALS, higher ccf-mtDNA indices tended to correlate with greater disease severity and more rapid functional decline. In addition, higher plasma and CSF D-loop/COX3 ratios showed marginal trends toward association with faster disease progression.
CONCLUSIONS: This study systematically characterizes mtDNA alterations in whole blood, plasma and CSF samples of ALS, offering new insights into mtDNA involvement in neurodegeneration.

Keywords:  Amyotrophic lateral sclerosis (ALS); Circulating cell-free mitochondrial DNA (ccf-mtDNA); Mitochondrial dysfunction; mtDNA copy number

DOI:  https://doi.org/10.1016/j.jns.2026.125797
Cells. 2026 Feb 20. pii: 372. [Epub ahead of print]15(4):

Mitochondria at the Crossroads of Cardiovascular Disease: Mechanistic Drivers and Emerging Therapeutic Strategies.

Sonila Alia, Gaia Pedriali, Paolo Compagnucci, Yari Valeri, Valentina Membrino, Tiziana Di Crescenzo, Elena Tremoli, Laura Mazzanti, Arianna Vignini, Paolo Pinton, Michela Casella.

  Mitochondria are central regulators of cardiac homeostasis, integrating energy production, redox balance, calcium handling, and innate immune signaling. In cardiovascular disease (CVD), mitochondrial dysfunction acts as a unifying mechanism connecting oxidative stress, metabolic inflexibility, inflammation, and structural remodeling. Disturbances in mitochondrial quality control-encompassing fusion-fission dynamics, PINK1/Parkin- and receptor-mediated mitophagy, biogenesis, and proteostasis-compromise mitochondrial integrity and amplify cardiomyocyte injury. Excess reactive oxygen species, mitochondrial DNA release, and calcium overload further activate cGAS-STING, NLRP3 inflammasomes, and mPTP-driven cell death pathways, perpetuating maladaptive remodeling. Therapeutic strategies targeting mitochondrial dysfunction have rapidly expanded, ranging from mitochondria-targeted antioxidants (such as MitoQ and SS-31), nutraceuticals, metabolic modulators (SGLT2 inhibitors, metformin), and mitophagy or biogenesis activators to innovative approaches including mtDNA editing, nanocarrier-based delivery, and mitochondrial transplantation. These interventions aim to restore organelle structure, improve bioenergetics, and reestablish balanced quality control networks. This review integrates recent mechanistic insights with emerging translational evidence, outlining how mitochondria function as bioenergetic and inflammatory hubs in CVD. By synthesizing established and next-generation therapeutic strategies, it highlights the potential of precision mitochondrial medicine to reshape the future management of cardiovascular disease.

Keywords:  cardiovascular disease; inflammation; mitochondrial dysfunction; mitochondrial quality control; mitochondrial signaling; mitophagy; oxidative stress

DOI:  https://doi.org/10.3390/cells15040372
Int J Mol Sci. 2026 Feb 22. pii: 2053. [Epub ahead of print]27(4):

Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?

María Beatriz Durán Alonso.

  Autophagy plays a key role in the development and homeostasis of the cochlear organ. Alterations in the autophagic pathways have been associated with damage to auditory cell types and hearing impairment caused by an array of factors like age, ototoxicity, exposure to high levels of noise, or genetic mutations. Cochlear damage frequently entails mitochondrial dysfunction, impaired mitophagy and the accumulation of high concentrations of free radicals. This review summarizes the observations made to date on the autophagic function in response to cochlear damage and the results of either activating or inhibiting these processes. The data demonstrate that autophagic activity is cell context-dependent and varies according to the cochlear cell type, the toxic agent, its levels and the length and timing of its administration; other factors that influence the autophagic response may be external to the auditory system or related to epigenetic changes or the expression of genetic variants. Modulation of the autophagic status has an effect on auditory cell loss and the progression to hearing impairment and this approach has thus become a promising avenue towards the protection of the hearing function. Nonetheless, this is no easy task and it will require the identification of reliable biomarkers to evaluate the dynamics of autophagic activity as well as the development of specific autophagy modulators that do not exert toxicity.

Keywords:  aging; autophagy; hearing loss; mitophagy; ototoxicity

DOI:  https://doi.org/10.3390/ijms27042053
Neuro Oncol. 2026 Feb 23. pii: noag038. [Epub ahead of print]

Mitochondria transfer in Glioblastoma.

Simon Storevik, Mina Thue Augustsson, Shannon Moreino, Hanjo Köppe, Dionysios C Watson, Defne Bayik, Carolina De La Pena Fernandez, Amanda M Serapiglia, Nikhil Panicker, Justin Lathia, Hrvoje Miletic.

  Glioblastoma (GBM) is a highly aggressive and metabolically adaptable brain tumor characterized by profound cellular heterogeneity and therapy resistance. Recent research has uncovered the phenomenon of horizontal mitochondrial transfer (HMT) between GBM cells and their microenvironment, particularly astrocytes, which contributes to tumor progression, metabolic reprogramming, and treatment resistance. This review summarises current knowledge on mitochondrial exchange in GBM via tunneling nanotubes (TNTs), tumor microtubes (TMs) and potentially via extracellular vesicles (EVs). It also explores the functional consequences of HMT, including enhanced oxidative phosphorylation (OXPHOS), increased tumorigenicity, and altered therapeutic responses. This review highlights the need for further investigation into the molecular drivers and context-specific outcomes of mitochondrial transfer in GBM, with implications for novel therapeutic strategies.

Keywords:  Glioblastoma; OXPHOS; mitochondria transfer; tumor microtubes; tunneling nanotubes

DOI:  https://doi.org/10.1093/neuonc/noag038