bims-mitrat 2026-07-19 papers

J Physiol. 2026 Jul 15.

Mitochondrial transplantation and neuromuscular recovery after skeletal muscle injury.

Sina Hadipour-Lakmehsari, Sara Al Mouaswas.

Keywords: injury; mitochondria; mitochondrial transplantation; skeletal muscle

Res Sq. 2026 Jul 06. pii: rs.3.rs-10105855. [Epub ahead of print]

Neuronal Mitochondrial Dysfunction Drives Astrocytic Mitochondrial Transfer after TBI: Reveals the Therapeutic Potential of astrocytic EV-Mito.

Gopal V Velmurugan, Hemendra J Vekaria, Alexander G Rabchevsky, Kai Saito, Josh M Morganti, Samir Patel, Brad Hubbard, Patrick G Sullivan.

Mitochondria are dynamic organelles essential for neuronal survival and synaptic function, and their dysfunction is a key consequence of excitotoxicity following traumatic brain injury (TBI). While intercellular mitochondrial transfer and exogenous mitochondrial transplantation have emerged as mechanisms to restore cellular bioenergetics, its in vivo relevance in the central nervous system remains incompletely understood. Here, we used astrocyte and neuron-specific mitochondrial reporters (GFP or Dendra2) in mice to assess cell-type-specific mitochondrial morphology, bioenergetics, and transfer 24hrs after TBI. Neurons exhibited marked mitochondrial dysfunction, including altered morphology and reduced bioenergetic capacity across somatic, synaptic, and non-neuronal fractions. In contrast, astrocytic mitochondria showed morphological changes but preserved bioenergetic function. Concomitantly, astrocyte-to-neuron mitochondrial transfer was significantly increased following injury, although transfer to synapses remained limited. Single-cell RNA sequencing of astrocytes revealed upregulation of genes involved in extracellular vesicle (EV) biogenesis and mitochondrial translation following injury compared to controls. In vitro co-culture studies confirmed that astrocytes transfer mitochondria to neurons via EVs containing mitochondria (EV-mito). Isolated EV-mito from astrocyte-conditioned media improves neuronal mitochondrial function under NMDA (N-methyl-D-aspartate) induced excitotoxic conditions. Together, these findings demonstrate that neuronal mitochondrial dysfunction drives astrocyte-mediated mitochondrial transfer as an adaptive neuroprotective response after TBI. This process preserves neuronal bioenergetics in the soma and neurites but not at synapses, highlighting both its therapeutic potential and spatial limitations.

DOI: https://doi.org/10.21203/rs.3.rs-10105855/v1

Exp Biol Med (Maywood). 2026 ;251 11128

Mitochondrial transfer and mesenchymal stem cells in ophthalmology: current evidence and therapeutic implications.

Xiaoli Liu, Mingqi Zhang, Zhuoshi Wang.

Mitochondrial dysfunction, driven by genetic mutations or oxidative stress, is a central contributor to the onset and progression of ophthalmic diseases. In recent years, intercellular mitochondrial transfer (MT) has emerged as a novel mechanism of cellular communication and repair in ocular tissues. MT occurs through tunneling nanotubes, extracellular vesicles (EVs), cell fusion, or transmitophagy, and has been shown to support photoreceptor survival, maintain retinal homeostasis, and protect against oxidative injury. Mesenchymal stem cells (MSCs), owing to their remarkable reparative and immunomodulatory properties, have attracted particular attention as efficient mitochondrial donors. Evidence from experimental models demonstrates that MSC-mediated MT can restore bioenergetics, mitigate oxidative stress, and rescue cellular function in inherited optic neuropathies, corneal injuries, retinal degenerative diseases, and ischemic retinopathies. This review summarizes current evidence of MT in ophthalmology, highlights the therapeutic contributions of MSCs, discusses the molecular and microenvironmental factors regulating MT efficiency, and outlines unresolved challenges. We further provide perspectives on how mitochondrial transfer may be translated into innovative therapies for ocular disorders.

Keywords: clinical translation; mesenchymal stem cells; mitochondrial transfer; ophthalmic diseases; retinal degeneration

DOI: https://doi.org/10.3389/ebm.2026.11128

J Vis Exp. 2026 Jun 26.

Exogenous Mitochondrial Transfer in Differentiating Brown Adipocytes and AGPAT2-Deficient Preadipocytes.

Antonio Moreno, Claudia Parra-Ruiz, Francisca Stolzenbach, Víctor Cortés.

Mitochondria are key signaling hubs; however, whether mitochondrial mass expansion is mechanistically required for differentiation remains an open question. AGPAT2 catalyzes the conversion of lysophosphatidic acid into phosphatidic acid, and its deficiency leads to adipose tissue deficiency and impaired adipogenesis associated with reduced mitochondrial mass. The impact of mitochondrial mass expansion on adipogenesis was assessed by transferring exogenous mitochondria into differentiating brown adipocytes. Whether mitochondrial transfer could rescue the impaired adipogenesis of AGPAT2-deficient cells was also investigated. Human and murine mitochondria were successfully transferred and incorporated into the endogenous mitochondrial network of differentiating mouse preadipocytes and persisted throughout brown adipogenesis. Adipogenic differentiation was required for the retention of transferred mitochondria. Mitochondrial transfer did not modify the expression of molecular markers of mature brown adipocytes or lipid droplet content, although it affected the relative distribution of lipid droplet size in a species-dependent manner. In Agpat2-/- preadipocytes, mitochondrial transfer failed to rescue adipogenesis, indicating that mitochondrial mass expansion alone is insufficient to reverse the mechanisms leading to lipodystrophy in this model. These results indicate that, although exogenous human and murine mitochondria can be incorporated into the mitochondrial network of differentiating adipocytes, they do not directly influence the adipogenic program.

DOI: https://doi.org/10.3791/71223

Adv Biol (Weinh). 2026 Jul;10(7): e70137

Context-Dependent Functional Outcomes of Mitochondrial Transfer: A Donor-Recipient Perspective.

Bin Wang, Tian Lin, Xinying Mo, Benson Peter Mugaka, Guangjie Tai, Ming Xu.

Intercellular mitochondrial transfer has emerged as a fundamental mechanism regulating tissue homeostasis and disease progression, yet its complex regulatory network remains incompletely understood. This review synthesizes the principal transfer mechanisms, focusing on tunneling nanotube (TNT)-mediated direct contact and extracellular vesicle (EV)-mediated indirect transport. Based on the functional disparity between donor and recipient cells, we categorize four prototypical pairing modes and delineate the functional diversity of mitochondrial transfer in metabolic support, tissue repair, and stress responses. Building on this framework, we propose five key determinants as the core dimensions for understanding transfer efficiency and functional outcomes across various contexts: donor mitochondrial quality, donor transfer capacity, recipient metabolic demand, recipient integration capacity, and donor-recipient compatibility. Integrating these factors provides a conceptual basis for explaining the dual effects of mitochondrial transfer-supporting tissue regeneration and functional recovery while, in certain microenvironments, driving pathological reprogramming. This review offers a comprehensive framework for mechanistic studies and clinical translation of mitochondrial transfer and highlights its therapeutic potential in regenerative medicine, aging intervention, and cancer therapy.

Keywords: cell communication; extracellular vesicles; metabolic reprogramming; mitochondria; tumor microenvironment; tunneling nanotubes

DOI: https://doi.org/10.1002/adbi.70137

Cell Commun Signal. 2026 Jul 14.

Free mitochondrial transfer enhances bone regeneration through cathepsin H mediated cysteine cycle.

Jiayong Diao, Qixuan He, Quanzhen Liu, Yuxuan Liu, Simiao Chen, Yuzhe Zhang, Houda Gui, Jingyi Chen, Dongni Wu, Xinyu Pang, Qingyue Zhang, Ya-Nan Wang, Dongjiao Zhang.

BACKGROUND: Mitochondria, as crucial organelles in eukaryotic cells, are deeply involved in cellular energy metabolism and biogenesis. Currently, mitochondria have been found to transfer between cells and regulate a range of cellular functions and research has found that mitochondrial transfer has been shown to play an important role in regulating bone homeostasis.
METHODS: Laser confocal imaging was used to confirm the occurrence of mitochondrial transfer between cells. JC-1 staining explains the state of free mitochondria in receptor cells. In order to reveal the relationship between the state and function of free mitochondria, osteogenic induction, Western blotting, flow cytometry, and in vivo experiments were conducted. RNA seq is used to analyze changes in cells. Different inhibitors were used to verify the specific mechanism of action of free mitochondrial transfer.
RESULTS: Free mitochondrial transfer can improve the function of receptor cells through lysosomal pathway. Free mitochondria are degraded by cathepsin H (Ctsh) in lysosomes and release a large amount of cysteine after entering the receptor cells. In this process, the existence of membrane potential of free mitochondria is not critical. Cysteine, as the most important raw material for glutathione synthesis, can enhance the number and function of mitochondria in receptor cells.
CONCLUSION: Our study demonstrates that free mitochondrial transfer promotes bone regeneration by increasing cysteine supply, and provides innovative insights for understanding mitochondrial transfer.

Keywords: Bone regeneration; Cathepsin H; Cysteine; Free mitochondrial transfer; Lysosome; Mitochondria

DOI: https://doi.org/10.1186/s12964-026-03060-2