bims-mitrat Biomed News
on Mitochondrial transplantation and transfer
Issue of 2026–02–01
six papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇
  1. Mitochondria transfer from myocytes to endothelial cells Promotes angiogenesis in skeletal muscle.
  2. Transplantation of Mitochondria isolated from iPSC-MSCs mitigates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence.
  3. Viable exogenous mitochondria modulate neurochemical and behavioral features of fibromyalgia in a reserpine-induced fibromyalgia model.
  4. Circulating Mitochondrial Transfer Carrying Dihydroorotate Dehydrogenase Reduces Oxidative Cell Death in Prolonged Cold-induced Cardiac Reperfusion Injury in Heart Transplantation.
  5. Mitochondrial DAMPs as a critical driver in the development of acute graft versus host disease and emerging mitochondria targeted therapeutic strategies.
  6. Exogenous mitochondrial transfer alleviates neurodegeneration in Parkinson's disease model by improving mitochondrial function.
  1. Mitochondrion. 2026 Jan 24. pii: S1567-7249(26)00006-1. [Epub ahead of print] 102116
    Mitochondria transfer from myocytes to endothelial cells Promotes angiogenesis in skeletal muscle.
    Yu-Feng Long, Ai-Jun Huang, Shuo Tang, Zhen Xu, Ming-Yue Wu, Kai Liu, Ze-Cai Chen, Lei Qin, Bing-Yang Dai, Cheng Dong, Wing-Hoi Cheung, Xin-Luan Wang, Da-Zhi Yang.
      Skeletal muscle and vascular health are closely interconnected, yet the mechanisms underlying their crosstalk remain poorly understood. This study investigates the role of mitochondria transfer from myocytes to endothelial cells. Using in vitro 2D and 3D coculture systems, combined with protein-level and functional analyses, we show that mitochondria are transferred via extracellular vesicles in a Rab7-dependent and cellular connection-independent manner. Connexin 43 (CX43) inhibition downregulating Growth-Associated Protein 43 (GAP43) but enhances mitochondria transfer, accompanied by increasing Rab7. Transferred mitochondria promote endothelial cells proliferation, migration, ATP production, and angiogenesis, which could be the key processes in preserving vascular integrity and muscle function. Our study indicated that the aging-associated decline in CX43 and mitochondrial quality exacerbates muscle atrophy by facilitating the transfer of dysfunctional mitochondria. These findings uncover a novel mechanism of muscle-vessel communication and highlight mitochondria transfer as a potential therapeutic target for aging-related muscular and vascular deterioration. New and Noteworthy. Mitochondria transfer is a way for cell communication. However, mitochondria transfer between myocyte and endothelial cell remains unknown. Here, we demonstrates that mitochondria transfer occurs between myocytes and endothelial cells. Interestingly, inhibition of CX43 leads to a decrease in GAP43 expression, while simultaneously upregulating Rab7 and enhancing mitochondria transfer from myocytes to endothelial cells. Furthermore, we reveal that Rab7-induced mechanism mediates the transfer of both functional and impaired mitochondria from myocytes to endothelial cells.
    Keywords:  Endothelial cells; Mitochondria transfer; Muscle; Myocytes; Vessel
    DOI:  https://doi.org/10.1016/j.mito.2026.102116
  2. Free Radic Biol Med. 2026 Jan 23. pii: S0891-5849(26)00038-9. [Epub ahead of print]
    Transplantation of Mitochondria isolated from iPSC-MSCs mitigates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence.
    Qi Yang, Shibing Zhao, Junxiu Zhao, Ying Shen, Yimei Hong, Jie Qiu, Ziqi Li, Fang Lin, Kexin Ma, Bei Hu, Yuelin Zhang, Xiaoting Liang.
       BACKGROUND: Mitochondrial dysfunction plays an important role in the development of doxorubicin-induced cardiomyopathy (DIC). Mitochondrial transplantation (MT) exerts beneficial effects on multiple cardiovascular diseases.
    OBJECTIVE: This study aimed to determine whether transplantation of exogenous mitochondria derived from induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSC-Mito) could protect against DIC in mice and explore the potential molecular mechanisms.
    METHODS: Mitochondria were isolated from iPSC-MSCs using ultracentrifugation, then characterized by transmission electron microscopy and Western blotting. The cellular senescence of neonatal mouse cardiomyocytes (NMCMs) was examined by senescence-associated-β-galactosidase assay. Mitochondrial function in doxorubicin (DOX)-treated NMCMs exposed to different treatments was evaluated by seahorse assay. A mouse model of DIC was induced by intraperitoneal injection of DOX followed by intraperitoneal injection of iPSC-MSC-Mito. Cardiac function, fibrosis and cardiomyocyte senescence in each group was examined.
    RESULTS: The isolated iPSC-MSC-Mito exhibited intact mitochondrial morphology and quality. In vitro, iPSC-MSC-Mito could be internalized by NMCMs under DOX challenge. Administration of iPSC-MSC-Mito improved the respiratory capacity of cardiomyocytes under DOX challenge, due to downregulated lactate level, leading to inhibition of cardiomyocyte senescence. This effect was partially abrogated by exogenous lactate. Utilizing molecular docking and site-directed mutation assays, we found that lactate regulated SIRT2 expression by binding to the ARG97 and HIS187 residues in the PH domain of SIRT2. In vivo, transplantation of iPSC-MSC-Mito functionally attenuated DIC, manifested as improved cardiac function and decreased cardiac fibrosis and cardiomyocyte senescence.
    CONCLUSIONS: Transplantation of mitochondria isolated from iPSC-MSCs improved cardiac function in a mouse model of DIC by alleviating cardiomyocyte senescence via improved metabolic function. This may offer a novel therapeutic strategy for DIC.
    Keywords:  Cardiomyopathy; Doxorubicin; Mitochondrial transplantation; Senescence; iPSC-MSCs
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.01.030
  3. Life Sci. 2025 Dec 01. pii: S0024-3205(25)00684-8. [Epub ahead of print]382 124048
    Viable exogenous mitochondria modulate neurochemical and behavioral features of fibromyalgia in a reserpine-induced fibromyalgia model.
    Nourhan S Elkholy, Haitham S Mohammed, Ayman Saber Mohamed, Abdou Kamal Allayeh, Ahmed M Al-Abd.
      Fibromyalgia Syndrome (FMS) is a chronic disorder marked by widespread pain, fatigue, and cognitive dysfunction, often associated with mitochondrial dysfunction and oxidative stress. Despite existing treatments, none address the underlying mitochondrial defects. This study investigates the potential of viable exogenous mitochondria, isolated from H9C2 (2-1) myocardial cells, as a preclinical therapeutic and regenerative intervention for FMS in a reserpine-induced fibromyalgia rat model. Three doses (0.15, 0.5, and 1.5 mg/kg) of mitochondria were prepared and characterized using electron microscopy, dynamic light scattering, and flow cytometry for their integrity and viability. The different doses were intravenously administered in reserpine-induced FM female rats to determine the optimal therapeutic dosage. Key findings demonstrated dose-dependent effects on FM-related markers such as nociceptive response latency, blood serum assays, oxidative stress biomarkers, and neurotransmitter levels. A biodistribution study revealed preferential accumulation of mitochondria in affected tissues, such as the brain and soleus muscle, suggesting targeted delivery and potential regenerative effects. These findings provide preliminary preclinical evidence supporting mitochondrial transplantation as a novel and effective regenerative therapy for addressing mitochondrial dysfunction in fibromyalgia, suggesting a promising direction for future research on interventions targeting chronic pain and metabolic dysfunction.
    Keywords:  Biodistribution; Exogenous mitochondria; Fibromyalgia; Mitochondrial dysfunction; Neurotransmitters; Oxidative stress; Reserpine model
    DOI:  https://doi.org/10.1016/j.lfs.2025.124048
  4. Transplantation. 2026 Jan 28.
    Circulating Mitochondrial Transfer Carrying Dihydroorotate Dehydrogenase Reduces Oxidative Cell Death in Prolonged Cold-induced Cardiac Reperfusion Injury in Heart Transplantation.
    Zhaohua Yang, Dajun Zhao, Yijun Huang, Chengzhi Han, Maoxiang Chen, Fanshun Wang, Shouguo Yang, Chunsheng Wang, Shutian Zhang.
       BACKGROUND: Prolonged cold myocardial ischemia/reperfusion injury-driven by mitochondrial dysfunction, oxidative stress, and ferroptosis-limits cardiac transplantation success. Dihydroorotate dehydrogenase (DHODH), a key mitochondrial enzyme for redox homeostasis and ferroptosis suppression, has short ischemic half-life and poor targeting, restricting clinical use. We aimed to engineer cardiomyocyte-targeted mitochondria (DHODH-CT-Mito) for sustained DHODH delivery to mitigate prolonged cold myocardial ischemia/reperfusion.
    METHODS: Using a Langendorff model, we validated DHODH's transient protective role. DHODH-CT-Mito was designed by fusing translocase of the outer mitochondrial membrane 20 with an ischemic myocardium-targeting peptide. Efficacy/safety were tested in a 2-mo rat allogeneic heart transplant model, assessing homing, membrane potential, immunogenicity, biodistribution, and sustained DHODH activity.
    RESULTS: DHODH-CT-Mito showed robust myocardial homing, preserved membrane potential, and sustained DHODH activity. Treated grafts had improved long-term function, less fibrosis, and reduced apoptosis. It displayed low immunogenicity (transient inflammation, balanced macrophages) and minimal off-target accumulation. Acute DHODH delivery primed grafts for sustained redox balance.
    CONCLUSIONS: DHODH-CT-Mito overcomes exogenous DHODH limits, providing durable mitochondrial activity, suppressing ferroptosis, and preserving graft function with low risk-offering a translatable strategy for donor heart preservation.
    DOI:  https://doi.org/10.1097/TP.0000000000005622
  5. Front Immunol. 2025 ;16 1740433
    Mitochondrial DAMPs as a critical driver in the development of acute graft versus host disease and emerging mitochondria targeted therapeutic strategies.
    Vasantharaja Raguraman, Yogamaya Divakar Prabhu, Gopal Viswanathan Velmurugan, Gerhard C Hildebrandt, Senthilnathan Palaniyandi.
      Mitochondrial fusion and fission regulate mitochondrial morphology and homeostasis, both of which are essential for maintaining cellular health. Free mitochondria and mitochondrial-containing extracellular vesicles have emerged as key mediators of pathological processes. Conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) damage and lead to impaired mitochondrial function, including biogenesis and respiration, as well as elevated reactive oxygen species (ROS), which contribute to the development of inflammatory conditions as well as activation of antigen presenting cells, the latter being key players in acute graft versus host pathophysiology (GVHD). This leads to increased T-cell activation and proliferation, which increases alloreactivity and drives GVHD. Dysregulated mitochondrial dynamics lead to the release of mitochondrial DNA and formylated peptides, which act as Damage-Associated Molecular Patterns (DAMPs) and trigger cellular homeostatic imbalances, ultimately leading to more inflammation. The understanding that mitochondrial dysfunction contributes to GVHD offers novel therapeutic strategies, including blocking DAMP signaling and modulating immune cell metabolism to restore mitochondrial health. This review aims to understand mitochondrial homeostasis in both recipient and donor cells. This is crucial for understanding GVHD pathophysiology and developing mitochondria-targeted therapies or mitochondrial transfer strategies as potential therapeutic interventions for GVHD.
    Keywords:  DAMP (Damage Associated Molecular Pattern); Graft versus host disease (GVHD); hematopoietic cell transplantation (HCT); mitochondria transfer; mitochondrial DNA
    DOI:  https://doi.org/10.3389/fimmu.2025.1740433
  6. Mitochondrion. 2026 Jan 26. pii: S1567-7249(26)00001-2. [Epub ahead of print]87 102111
    Exogenous mitochondrial transfer alleviates neurodegeneration in Parkinson's disease model by improving mitochondrial function.
    Yu Si, Muhammad Abid Hayat, Yingyin Ni, Jingwen Zhang, Tao Guo, Yudie Cao, Yancheng Hong, Hao Zuo, Xin Sun, Zheng Li, Bo Chen, Jia Wan, Yong Wang, Jiabo Hu.
      Parkinson's disease (PD) is the second most common neurodegenerative disorder related to mitochondrial dysfunction. Recent studies have reported that mitochondrial transfer between cells occurred naturally and was effective for alleviating mitochondrial dysfunction. In the current study, functional exogenous mitochondria (Mito) were extracted and administered to both in vitro and in vivo PD models, exploring the therapeutic effects of Mito on damaged neurons. It was observed that in the in vitro PD model, Mito improved cell morphology and increased cell viability from 25.06% to 42.44% (p < 0.001), while enhancing mitochondrial activity within the cells by a 201% increase in the JC-1 red/green fluorescence ratio (p = 0.02). Further analysis suggests that Mito's neuroprotective effects are potentially mediated via integrated modulation of neuroinflammation and ferroptosis pathways. The findings of the in vivo PD model showed that Mito improved motor coordination in the rotational test by 71% (p < 0.01) and ameliorated depression-like behavior demonstrating a 13.4% enhancement in Sucrose preference (p < 0.001), accompanied by histological evidence of neuroprotection observed in Nissl-stained brain sections and the significant recovery in mitochondrial function by 31.6% (p = 0.01). This study is the first to demonstrate that Mito can enter a PD cell model and rescue neuronal and mitochondrial damage in both in vivo and in vitro settings, with transcriptomic analysis revealing the involvement of key molecular pathways related to neuroinflammation and ferroptosis. This offers new insights and prospectus therapeutic strategies for PD as well as a foundation for future research in clinical medicine.
    Keywords:  Mitochondria; Mitochondrial transplantation; Neurodegenerative diseases; Neurons; Parkinson’sdisease
    DOI:  https://doi.org/10.1016/j.mito.2026.102111
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