bims-mitrat Biomed News
on Mitochondrial transplantation and transfer
Issue of 2025–07–20
six papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute



  1. Function (Oxf). 2025 Jul 17. pii: zqaf031. [Epub ahead of print]
      The fusion of skeletal muscle stem cell (MuSC) to myofibers during hypertrophy has exclusively focused on the transfer of the MuSC nucleus, leaving the fate of other MuSC organelles, such as mitochondria, largely unexplored. The objective of this study was to determine if MuSCs transfer their mitochondria upon myofiber fusion in response to a hypertrophic stimulus. To achieve this goal, we specifically labeled MuSC mitochondria with Dendra2 fluorescence by crossing the MuSC-specific CreER (Pax7CreER/CreER) mouse with the Rosa26-Dendra2 mouse to generate the Pax7-Dendra2 mouse. To induce the fusion of MuSC to myofibers, Pax7-Dendra2 mice underwent synergist ablation surgery to induce mechanical overload (MOV) of plantaris muscle for 3, 7 and 14 days. To track MuSC proliferation, a mini-osmotic pump was implanted at the time of MOV to continuously deliver EdU. At the designated time, plantaris muscles were excised and processed for immunohistochemistry to quantify Dendra2 + myofibers. There was a progressive increase in Dendra2-positive fibers across the MOV time course. Three distinct patterns or domains of Dendra2 fluorescence within myofibers were identified and designated as newly fused (NF), crescent (CS) or diffuse (DF). From these Dendra2 + domain types, we inferred MuSC fusion dynamics which indicated MuSC fusion occurred prior to mechanical overload day 3 (MOV-3) and preferentially with Type 2A fibers. Quantification of EdU + myonuclei found the majority of early (MOV < 3 days) MuSC fusion was division-independent, while proliferating MuSCs contributed primarily to later fusion events. The results of this study provide the first evidence that MuSC mitochondria are transferred to myofibers upon fusion during hypertrophy while, unexpectedly, revealing a greater complexity in MuSC fusion than previously recognized.
    Keywords:  mitochondrial transfer; muscle stem cell; satellite cell; stem cell dynamics; stem cell fusion
    DOI:  https://doi.org/10.1093/function/zqaf031
  2. Curr Opin Hematol. 2025 Jul 15.
       PURPOSE OF REVIEW: There is an increasing recognition that mitochondria are dynamic regulators of cell fate. Mitochondria transplantation has emerged as a promising therapeutic strategy for conditions ranging from metabolic disorders to neurodegenerative diseases. Thus, there is a growing need for scalable mitochondrial sources for transplantation. We highlight megakaryocytes, best known for their role in platelet production, as a novel and versatile candidate source for mitochondria transplantation.
    RECENT FINDINGS: Megakaryocytes are naturally equipped to package and deliver functional mitochondria when producing platelets. Furthermore, MKs can share their mitochondria with neighboring cells in the bone marrow. Given the abundance of mitochondria in megakaryocytes, they may represent an ideal source of mitochondria for transplantation. A better understanding of the role of mitochondria in megakaryocyte heterogeneity and metabolic functions may help harness megakaryocytes for therapeutic transplantation applications.
    SUMMARY: Megakaryocyte-derived mitochondria transplantation offers a promising avenue for treating metabolic disorders, leveraging existing mechanisms. Future research should address limitations in megakaryocyte biogenesis and heterogeneity, and optimize delivery systems to maximize therapeutic efficacy.
    Keywords:  cell therapy; megakaryocytes; mitochondria transplantation
    DOI:  https://doi.org/10.1097/MOH.0000000000000889
  3. J Proteomics. 2025 Jul 09. pii: S1874-3919(25)00118-6. [Epub ahead of print]320 105491
      One of the mechanisms of intercellular communication is the transfer of proteins and organelles among cells. This has been observed in diverse phylogenetic groups, and can be mediated by extracellular vesicles, like exosomes or exophores, tunneling nanotubes, pores like plasmodesmata or processes like trogocytosis. The vast majority of studies in this field have used confocal microscopy and flow cytometry to detect proteins from donor cells in recipient cells. Proteomics has not been widely used, despite the fact that efficient tools are available for the labeling, enrichment and unbiased large-scale identification of the transferred proteins. Among these tools are trans-SILAC, affinity capture-MS/MS, BONCAT, TransitID and the use of cells from different species. In this review we describe illustrative examples of the intercellular transfer of proteins and mitochondria indicating the experimental methodologies used, both proteomics and non-proteomics, and emphasizing the capabilities of the mass spectrometry-based strategies.
    Keywords:  Affinity capture-MS/MS; BONCAT; Extracellular vesicles; Mass spectrometry; Plasmodesmata; Trans-SILAC; TransitID; Trogocytosis; Tunneling nanotubes
    DOI:  https://doi.org/10.1016/j.jprot.2025.105491
  4. Cell Commun Signal. 2025 Jul 16. 23(1): 341
       BACKGROUND: Deficits in mitochondrial bioenergetics and dynamics are strongly implicated in the selective vulnerability of striatal neurons in Huntington´s disease. Beyond these neuron-intrinsic factor, increasing evidence suggest that non-neuronal mechanisms, particularly astrocytic dysfunction involving disrupted homeostasis and metabolic support also contribute to disease progression. These findings underscore the critical role of metabolic crosstalk between neurons and astrocytes in maintaining striatal integrity. However, it remains unclear whether this impaired communication affects the transfer of mitochondria from astrocytes to striatal neurons, a potential metabolic support mechanism that may be compromised in Huntington´s Disease.
    METHODS: Primary striatal astrocytes were obtained from wild-type and R6/1 mice to investigate mitochondrial dynamics. Expression levels of key mitochondrial fusion and fission proteins were quantified by Western blotting and RT-PCR. Mitochondria morphology, oxidative stress and membrane potential were assessed using confocal microscopy following staining with mitochondria-specific dyes. Mitochondrial respiration was measured using the Oxygraph-2k respirometer system (Oroboros Instruments). Transmitophagy was evaluated by confocal imaging after labeling astrocytic mitochondria with Mitotracker dyes. To assess the functional impact of mitochondrial transfer on neurons, Sholl analysis, neuronal death and oxidative stress levels were quantified using specific fluorogenic probes.
    RESULTS: Striatal astrocytes from HD mice exhibited a significant increase in mitochondrial fission, and mitochondrial oxidative stress, mirroring alterations previously reported in striatal neurons. Analysis of mitochondrial oxygen consumption rate (OCR) revealed elevated respiration activity and enhanced ATP-linked respiration, indicative of a hypermetabolic state. Concurrently, increased lactate production suggested a shift toward dysregulated astrocytic energy metabolism. These mitochondrial alterations were functionally detrimental: astrocytic mitochondria derived from HD mice when taken up by striatal neurons via transmitophagy, led to reduced neuronal branching and disrupted oxidative homeostasis.
    CONCLUSIONS: Our findings demonstrate that striatal astrocytes from HD mice exhibit a hypermetabolic phenotype, characterized by increased mitochondrial respiration, disrupted mitochondrial dynamics, and elevated mitochondrial oxidative stress. Importantly, we identify a novel mechanism of astrocyte-neuron interaction involving the transfer of dysfunctional mitochondria from astrocytes to neurons. The uptake of these compromised mitochondria by striatal neurons results in reduced neuronal branching and increased reactive oxygen species (ROS) production. Collectively, these results highlight the pathological relevance of impaired astrocyte-to-neuron mitochondrial transfer and emphasize the contributory role of astrocytic dysfunction in Huntington´s disease progression.
    Keywords:  Astrocytes; Huntingtin; Mitochondria transfer; Neuroglial communication; R6/1 mice; Striatum
    DOI:  https://doi.org/10.1186/s12964-025-02341-6
  5. J Transl Med. 2025 Jul 14. 23(1): 789
      This review explores the significant potential of mitochondrial transplantation (MT) in enhancing outcomes for DCD heart transplantation, particularly in mitigating ischemia-reperfusion injury (IRI). MT restores mitochondrial function and ATP production, thereby improving myocardial contractility and counteracting the energy depletion and oxidative stress that jeopardize the viability of DCD grafts. Furthermore, the synergistic application of MT with extracorporeal perfusion significantly enhances graft viability by reducing metabolic waste accumulation and modulating the inflammatory response during prolonged preservation. Studies show that MT decreases reactive oxygen species (ROS) levels, enhances antioxidant enzyme activity, and regulates immune activation, ultimately improving graft survival. Notably, MT has shown promising results in maintaining heart function during extended perfusion, delaying functional loss due to energy depletion. Despite encouraging preclinical findings, additional clinical validation is required, particularly in DCD heart transplantation, to confirm its potential in improving long-term graft function and expanding the donor pool in high-risk scenarios.
    Keywords:  Donation after circulation death; Heart transplantation; Ischemic reperfusion injury; Mitochondrial; Mitochondrial transplantation
    DOI:  https://doi.org/10.1186/s12967-025-06805-8
  6. Bioact Mater. 2025 Oct;52 845-856
      Mitochondrial transplantation promotes cardiac repair following injury; however, its effects on limb ischemia due to peripheral artery disease (PAD) remain unclear. In this study, transplantation with mitochondria isolated from both murine muscle tissue and human arterial blood significantly promotes revascularization and blood flow recovery in a hindlimb ischemia mouse model. Our findings further show that transplanted mitochondria promote macrophages infiltrating into ischemic regions. Additionally, internalization of the mitochondria promotes macrophage M2-like polarization, resulting in increased pro-angiogenic factors expression and secretion and subsequent endothelial cell and smooth muscle cell proliferation. In conclusion, mitochondrial transplantation shows considerable potential in improving peripheral ischemia and provides therapeutic options for patients with PAD.
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.06.050