bims-mitrat 2026-01-18 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–01–18
eight papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Intercellular mitochondrial transfer rewires redox signaling and metabolic plasticity: mechanisms, disease relevance and therapeutic frontiers.
Mitochondrial transfer: a Janus-faced force in health and disease.
Mitochondrial transfer in cancer: mechanisms, immune evasion, and therapeutic opportunities.
Unveiling the neuroprotective power of mitochondrial transfer in orofacial inflammatory pain through ER membrane remodeling.
Dental Pulp Stem Cells Orchestrate Macrophage Polarisation in Pulpitis via Mitochondrial Transfer.
Iron oxide nanoparticles-driven mitochondrial renewal rejuvenates the aged bone marrow niche.
Mitochondrial transfer from immune to tumor cells enables lymph node metastasis.
The need to understand the underlying mechanisms associated with mitochondrial therapies in assisted reproduction before further clinical trials are performed.

Redox Biol. 2026 Jan 09. pii: S2213-2317(26)00017-0. [Epub ahead of print]90 104019

Intercellular mitochondrial transfer rewires redox signaling and metabolic plasticity: mechanisms, disease relevance and therapeutic frontiers.

Jiahui Wang, Rongqing Li, Li Qian.

  Intercellular mitochondrial transfer is recognized as a central mechanism that shapes redox homeostasis, metabolic plasticity, and cellular resilience across multiple tissues. Through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junction channels (GJCs), and cell fusion, mitochondria move between donor and recipient cells to restore bioenergetic capacity, buffer oxidative stress, and tune redox-sensitive signaling networks. Recent work has begun to clarify the regulatory framework governing donor-recipient specificity, cargo selection, and the stress-activated cues that trigger organelle exchange. Mitochondrial transfer also exerts distinct, context-dependent influences on disease trajectories. It mitigates injury in neurological damage, ischemia-reperfusion conditions, immune dysfunction, aging, and inflammatory pain, largely by reprogramming mitochondrial function and reactive oxygen species (ROS) dynamics. Conversely, in cancer, mitochondrial acquisition enhances metabolic flexibility, invasiveness, and resistance to therapy. Current therapeutic approaches, including mitochondrial transplantation, EV-based delivery systems, and mitochondria-enhanced immune cells, highlight the translational potential of manipulating mitochondrial exchange, yet face challenges such as mitochondrial fragility, inefficient targeting, and immunogenicity. Deeper mechanistic insight into how mitochondrial transfer remodels redox signaling and metabolic adaptation will be essential for converting this biological process into next-generation organelle-level interventions for redox-driven disorders.

Keywords:  Extracellular vesicles (EVs); Immunometabolism; Mitochondrial therapeutics; Mitochondrial transfer; Tunneling nanotubes (TNTs)

DOI:  https://doi.org/10.1016/j.redox.2026.104019
J Transl Med. 2026 Jan 16. 24(1): 76

Mitochondrial transfer: a Janus-faced force in health and disease.

Yuan Hu, Wenqin Zhou, Lin Chen.



Keywords:  Immune evasion; Infections; Intercellular communication; Mitochondrial transfer; Organelle therapy; Tumor microenvironment

DOI:  https://doi.org/10.1186/s12967-025-07649-y
Genomics Inform. 2026 Jan 13.

Mitochondrial transfer in cancer: mechanisms, immune evasion, and therapeutic opportunities.

Hye In Ka, Hyun Goo Woo.

  Intercellular mitochondrial transfer (MT) is emerging as a transformative communication axis in cancer biology. Intact mitochondria or mitochondrial components can be exchanged between tumor cells, stromal elements, and immune cells via tunneling nanotubes, extracellular vesicles, cell fusion, or phagocytic uptake. This organelle exchange enables metabolic adaptation by restoring OXPHOS (oxidative phosphorylation), increasing ATP production, and enhancing survival in hostile environments. Conversely, tumor cells also hijack mitochondria from cytotoxic lymphocytes thereby undermining immune function and contributing to immune escape and tumor progression. These converging metabolic exchanges fuel immune evasion, metastatic potential, and resistance to chemotherapy, radiation, and immunotherapy. Cutting-edge tracing tools, including mitochondrial reporter proteins and single-cell mitochondrial genome lineage mapping, have uncovered MT events both in vitro and in vivo. Therapeutic strategies designed to block mitochondrial trafficking, inhibit nanotube formation or vesicle uptake, or enhance immune cell mitochondrial resilience hold promise for tumor sensitization and restoration of antitumor immunity. A deeper understanding of MT provides novel insight into cancer metabolism and intercellular communication, offering a foundation for future therapeutic innovation and potential clinical application as both a biomarker and a therapeutic target.

Keywords:  Cancer; Immune Evasion; Mitochondria; Mitochondrial Transfer

DOI:  https://doi.org/10.1186/s44342-025-00064-1
Cell Rep. 2026 Jan 13. pii: S2211-1247(25)01581-5. [Epub ahead of print]45(1): 116809

Unveiling the neuroprotective power of mitochondrial transfer in orofacial inflammatory pain through ER membrane remodeling.

Chen Li, Yike Li, Fei Liu, Boyao Lu, Shiyang Ye, Dexin Zhu, Muyun Wang, Junyu Chen, Cheng Zhou, Chunjie Li, Yanyan Zhang, Jiefei Shen.

  Neuro-glial mitochondrial transfer critically sustains neuronal function in disease. While this transfer reshapes inflammatory microenvironments, its pathological mechanisms in peripheral inflammatory pain remain uncharacterized, impeding targeted interventions. Here, employing primary satellite glial cells (SGCs)-trigeminal ganglion neurons (TGNs) co-culture models, we demonstrate that, during acute inflammation, SGCs transfer functional mitochondria to injured TGNs via tunneling nanotubes and free mitochondrial uptake. Inflammatory stress impairs mitophagy, leading to dysfunctional mitochondrial accumulation and heightened neuronal hyperexcitability. Mitochondria from SGCs restore mitophagic flux and enhance mitochondrial-endoplasmic reticulum (ER) contact sites, thereby facilitating calcium exchange and homeostasis while reducing neuronal hyperexcitability. Critically, Atl1 knockout and overexpression mice models reveal that ATL1-driven ER restructuring initiates autophagosome formation during mitophagy and regulates early-stage autophagic progression. Taken together, our findings uncover a neuroprotective axis wherein glial mitochondrial donation safeguards neurons, directly nominating mitochondrial dynamics for therapeutic intervention in orofacial inflammatory pain.

Keywords:  ATL1; CP: cell biology; CP: neuroscience; endoplasmic reticulum; inflammatory pain; mitochondrial transplantation; mitophagy; trigeminal ganglion

DOI:  https://doi.org/10.1016/j.celrep.2025.116809
Int Endod J. 2026 Jan 11.

Dental Pulp Stem Cells Orchestrate Macrophage Polarisation in Pulpitis via Mitochondrial Transfer.

Xiaoqian Gong, Lisha Zhu, Can Wang, Yu Wang, Yao Sun.

   AIM: Pulpitis represents a prevalent clinical condition in dentistry. Macrophages play pivotal roles in pulpitis immunopathology, while dental pulp stem cells (DPSCs) serve as key effectors in pulp tissue repair and immune regulation. Although mesenchymal stem cells are known to regulate immunity through mitochondrial transfer, this mechanism remains unexplored in pulpitis. This study investigated how mitochondrial transfer influences pulpitis progression and resolution.
METHODOLOGY: To investigate DPSC-macrophage mitochondrial transfer and its role in polarisation of macrophages, Lipopolysaccharide-stimulated cocultures were established. Transfer dynamics were analysed by fluorescence microscopy and flow cytometry. Macrophage polarisation (assessed via quantitative real-time polymerase chain reaction (qRT-PCR)/flow cytometry) in the cocultures was detected after mitochondrial transfer agonist/inhibitor treatment. Macrophage polarisation (assessed via qRT-PCR/flow cytometry) and mitochondrial function (reactive oxygen species production, membrane potential) were compared between mitochondria-receiving (Mito+) and non-receiving (Mito-) macrophages. Immunometabolic profiles (itaconate/succinate) were evaluated by qRT-PCR/immunofluorescence. Human dental pulp explants and experimental rat pulpitis models demonstrated the anti-inflammatory and reparative effects of mitochondrial transfer agonists. Data were analysed by one-way ANOVA and unpaired t-tests (α = 0.05).
RESULTS: Mitochondrial transfer from DPSCs to macrophages reduced during inflammation. Pharmacological inhibition of mitochondrial transfer exacerbated M1 macrophage polarisation, whereas its enhancement promoted M2 polarisation. Mito+ macrophages exhibited stronger M2 polarisation, improved mitochondrial function, and reduced itaconate/succinate metabolism compared to Mito- cells. Notably, using the inflamed dental pulp explant and the experimental rat pulpitis model, we demonstrated that augmenting mitochondrial transfer can effectively alleviate pulpitis and promote repair.
CONCLUSIONS: Mitochondrial transfer from dental pulp stem cells to macrophages via tunnelling nanotubes improved macrophage metabolic profiles. Enhanced mitochondrial transfer promoted M2 macrophage polarisation, thereby alleviating pulpal inflammation and promoting repair.

Keywords:  dental pulp stem cells; macrophage polarisation; metabolic reprogramming; mitochondrial transfer; pulpitis

DOI:  https://doi.org/10.1111/iej.70097
Biomaterials. 2026 Jan 12. pii: S0142-9612(26)00013-X. [Epub ahead of print]330 123989

Iron oxide nanoparticles-driven mitochondrial renewal rejuvenates the aged bone marrow niche.

Xiaoqing Sun, Xingyou Wang, Meihua Zhang, Shuyao Liu, Yue Zhu, Jing He, Yao Wu.

  With the aging population, treating age-related osteoporosis remains challenging due to the dysfunctional bone marrow microenvironment characterized by chronic inflammation, metabolic dysregulation, and impaired mitochondrial function in senescent cells. While mitochondrial transfer from macrophages to bone marrow mesenchymal stem cells (BMSCs) offers a promising therapeutic avenue, its efficacy is limited in aged niches where donor mitochondria exhibit functional deficits and poor recipient compatibility. We engineered KGM-PEG-SPIONs, functionalized Fe3O4 nanoparticles that enhance donor mitochondrial quality via autophagy activation and Fe-S cluster biogenesis, promote M2 macrophage polarization, and improve compatibility with the oxidative and inflammatory environment of senescent BMSCs. These M2-like mitochondria are transferred through connexin 43 gap junctions, restoring membrane potential, ATP production, calcium homeostasis, and osteogenic differentiation in recipient cells. In aged osteoporotic models, KGM-PEG-SPION-functionalized scaffolds remodel immune niches and promote bone formation. By integrating organelle quality control with environment-adapted mitochondrial transfer, this strategy surpasses approaches focusing solely on transfer quantity or polarization, establishing a programmable nanoplatform for organelle-based regeneration.

Keywords:  Autophagy; Fe–S cluster; Mitochondrial biogenesis; Mitochondrial transfer; Senescent macrophage polarization; Senile osteoporotic

DOI:  https://doi.org/10.1016/j.biomaterials.2026.123989
Cell Metab. 2026 Jan 12. pii: S1550-4131(25)00545-5. [Epub ahead of print]

Mitochondrial transfer from immune to tumor cells enables lymph node metastasis.

Azusa Terasaki, Keshav Bhatnagar, Alexis T Weiner, Yuhao Tan, Viktoria Szeifert, Han-Li Huang, Lukas Wiggers, Viviana Rodrigues, Cara C Rada, Vishnu Shankar, Suguru Saito, Peter Ofori Ankomah, Theodore Roth, Bill Chiu, Robert West, Lingyin Li, Nathan Reticker-Flynn, Jeffrey D Axelrod, Jonathan R Brestoff, Bo Li, Edgar Engleman, Derick Okwan-Duodu.

  Although the immune system is a significant barrier to tumor growth and spread, established tumors evade immune attack and frequently colonize immune populated areas such as the lymph node. The mechanisms by which cancer cells subvert the tumor-immune microenvironment to favor spread to the lymph node remain incompletely understood. Here, we show that, as a common attribute, tumor cells hijack mitochondria from a wide array of immune cells. Mitochondria loss by immune cells decreases antigen-presentation and co-stimulatory machinery, as well as reducing the activation and cytotoxic capacity of natural killer (NK) and CD8 T cells. In cancer cells, the exogenous mitochondria fuse with endogenous mitochondria networks, leak mtDNA into the cytosol, and stimulate cGAS/STING, activating type I interferon-mediated immune evasion programs. Blocking mitochondrial transfer machinery-including cGAS, STING, or type I interferon-reduced cancer metastasis to the lymph node. These findings suggest that cancer cells leverage mitochondria hijacking to weaken anti-tumor immunosurveillance and use the acquired mitochondria to fuel the immunological requirements of lymph node colonization.

Keywords:  MERCI; cGAS/STING; immune evasion; lymph node cancer metastasis; mitochondrial transfer

DOI:  https://doi.org/10.1016/j.cmet.2025.12.014
Hum Reprod. 2026 Jan 13. pii: deaf247. [Epub ahead of print]

The need to understand the underlying mechanisms associated with mitochondrial therapies in assisted reproduction before further clinical trials are performed.

Justin C St John, Raymond J Rodgers.

  Over a number of years, there has been growing interest in the introduction of more invasive ARTs, such as nuclear transfer, otherwise referred to as mitochondrial donation, and mitochondrial supplementation/transfer into clinical medicine. They have been proposed to overcome repeated failed fertilization or developmental arrest or to prevent carriers of mitochondrial DNA disease from having affected children. These technologies require considerable manipulation of the oocyte, which can affect its epigenetic programming that was established as it grew and developed into a fertilizable oocyte. Consequently, when a nucleus is transferred into an enucleated oocyte or pronuclei are transferred into an enucleated zygote, the nucleus must adapt to its new cytoplasmic environment in readiness for the waves of DNA demethylation and methylation that take place during preimplantation development. As a result, some key developmental gene networks are affected. Additionally, these approaches also affect patterns of mitochondrial DNA inheritance, with some embryos and offspring possessing mitochondrial DNA carried over into the oocyte with the nucleus, as well as the mitochondrial DNA from the donor oocyte. Similar outcomes result from the addition of extra mitochondrial DNA into oocytes through mitochondrial supplementation. We provide a background as to how these technologies evolved and discuss recent outcomes associated with clinical work so far undertaken within these approaches and their consequences for the offspring. We conclude that these technologies are not simply replacing or replenishing defective ooplasms with new or extra mitochondria but rather induce a series of genomic and epigenomic events that we do not yet fully understand. To our minds, these issues should be first addressed before clinical trials are continued.

Keywords:  embryo; metaphase II spindle transfer; mitochondrial DNA; mitochondrial donation; mitochondrial supplementation; mtDNA; nuclear transfer; oocyte; pronuclear transfer

DOI:  https://doi.org/10.1093/humrep/deaf247