bims-mitrat 2026-10-25 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–10–25
seven papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Mitochondrial transfer between breast cancer cells promotes ROS-dependent proliferation.
Mitochondrial transfer in solid tumors: dual roles in tumor progression and therapeutic targeting.
Rethinking mitochondrial isolation for the next generation of mitochondrial therapies.
Administration of injectable platelet-rich fibrin improved repair of thin endometrium via mitochondria in a rat model.
Systemic mitochondrial injection protects against methanol-induced optic neuropathy through restoration of mitochondrial function and attenuation of oxidative stress.
Extracellular Mitochondrial Components as Emerging Biomarkers and Therapeutic Targets in Human Diseases.
Mitochondrial subpopulations promote cellular responses to changes in metabolic demand and signal transduction.

bioRxiv. 2026 Aug 27. pii: 2026.08.26.747325. [Epub ahead of print]

Mitochondrial transfer between breast cancer cells promotes ROS-dependent proliferation.

Noah M Bressler, Taylor Z Stevens, Minna Roh-Johnson.

Previously, we showed that macrophages transfer mitochondria to breast cancer cells, promoting proliferation in acceptor cancer cells. Transferred mitochondria were depolarized and accumulated reactive oxygen species (ROS), and the mitochondrial transfer-induced proliferation was dependent upon ROS signaling (Kidwell et al. 2023). Our unexpected findings supported a model in which transferred mitochondria act as a signal for proliferation in acceptor cancer cells rather than a direct source of increased bioenergetics. It remains unclear whether this unexpected signaling mechanism is unique to macrophages as the donor cell, or whether this mechanism applies to mitochondrial transfer between other cells within the tumor microenvironment. Here, we show that highly metastatic cancer cells transfer mitochondria to weakly metastatic cancer cells. These transferred mitochondria are depolarized, accumulate ROS, and promote ROS-dependent proliferation in acceptor cancer cells. Furthermore, we specifically attribute this proliferative phenotype to the transfer of mitochondria, as when we isolate mitochondria from highly metastatic cells and apply these purified mitochondria directly to weakly metastatic cells in culture, acceptor cancer cells that internalize the purified mitochondria exhibit increased proliferation in a ROS-dependent manner. These findings support mitochondrial transfer within the breast tumor microenvironment as a signaling axis for proliferation, regardless of donor cell identity.

DOI: https://doi.org/10.64898/2026.08.26.747325
Extracell Vesicles Circ Nucl Acids. 2026 ;7(3): 1276-1296

Mitochondrial transfer in solid tumors: dual roles in tumor progression and therapeutic targeting.

Lirui Huang, Zeru Li, Cheng Qin, Bangbo Zhao, Tianyu Li, Yutong Zhao, Haoyu Shi, Xiangyu Zhang, Yiping Xie, Yutong Yan, Weibin Wang.

  Solid tumors account for the majority of cancer cases, and their incidence continues to increase. A solid tumor is not an isolated mass but interacts dynamically with cells in the tumor microenvironment. Mitochondria, which are essential for energy production and the regulation of apoptosis, play a critical role in cellular function and may serve as therapeutic targets. A growing body of evidence demonstrates that mitochondria can be transferred between cells via extracellular vesicles, tunneling nanotubes, gap junctions, and cell fusion. This process across various cell types, including stromal cells, immune cells, and cancer cells, and is enhanced under stress conditions, such as hypoxia and chemotherapy. Under these conditions, mitochondrial transfer enables tumor cells to acquire functional mitochondria from neighboring cells, thereby enhancing their metabolic plasticity and survival capacity. Mitochondrial transfer thus represents a critical adaptive mechanism that supports tumor progression. Targeting this dynamic form of intercellular communication offers a promising therapeutic strategy to overcome tumor metabolic plasticity, immunosuppression, and resistance to therapy.

Keywords:  Solid tumor; cell-to-cell communication; extracellular vesicles; mitochondrial transfer; tunneling nanotubes

DOI:  https://doi.org/10.20517/evcna.2026.68
Front Physiol. 2026 ;17 1975105

Rethinking mitochondrial isolation for the next generation of mitochondrial therapies.

Ethan A Simpson, Celina Phan, Jason P Acker.

  Mitochondrial isolation is fundamental to the study of mitochondrial biology and is increasingly relevant to emerging therapeutic applications such as mitochondrial transplantation. However, isolation procedures can substantially influence mitochondrial yield, purity, structural integrity, and bioenergetic function, making method selection an important determinant of experimental and translational outcomes. This review examines current mitochondrial isolation strategies, including physical disruption, chemical permeabilization, emerging microfluidic and automated dissociation technologies, and downstream separation approaches such as differential centrifugation, density-gradient centrifugation, filtration, and immunoaffinity enrichment. Each approach offers distinct advantages and limitations depending on the biological source, processing requirements, and intended application. Conventional methods remain widely used because of their accessibility and flexibility, but may introduce operator variability, mechanical stress, contamination, or loss of mitochondrial function. More selective purification strategies can improve sample purity, although often at the cost of additional processing time, technical complexity, and reduced recovery. Emerging technologies, including standardized mechanical dissociation and microfluidic disruption, may provide greater control over mitochondrial release, but require broader validation across tissues and sample volumes. A persistent challenge across isolation workflows is balancing mitochondrial recovery with preservation of organelle integrity and function. Future progress will require standardized, scalable isolation strategies that consistently preserve mitochondrial quality across different biological sources and downstream applications. Continued refinement of these approaches will be essential for advancing mitochondrial research and supporting the development of mitochondrial-based therapies.

Keywords:  bioprocessing; isolation; mitochondria; oxidative injury; stabilization

DOI:  https://doi.org/10.3389/fphys.2026.1975105
Stem Cell Res Ther. 2026 Jul 23. pii: 372. [Epub ahead of print]17(1):

Administration of injectable platelet-rich fibrin improved repair of thin endometrium via mitochondria in a rat model.

Haiqing Tian, Yixuan Zhu, Haozhe Ma, Nan Su, Manli Zhang, Xiaolin La, Lei Cui, Zijian Zhang, Jing Dong, Mengjie Zhang.

   BACKGROUND: Thin endometrium(TE) has been widely recognized as a critical factor contributing to reduced success rates of assisted reproductive technology (ART). In recent years, platelet-rich plasma (PRP) has been extensively employed in the treatment of thin endometrium; however, its underlying mechanisms remain poorly understood, and its clinical efficacy remains controversial. Given the superior therapeutic outcomes demonstrated by platelet concentrates (PCs) in regenerative medicine, the present study aimed to investigate the therapeutic potential and mechanistic basis of injectable platelet-rich fibrin (i-PRF) in an ethanol‑induced rat model of thin endometrium.
METHODS: i-PRF was prepared from human blood and characterized for growth factor release and microstructure. Rats were divided into control, Model, Ethanol + NS, and Ethanol+i-PRF groups.Endometrial morphology was assessed by H&E and immunohistochemistry. Receptivity was evaluated by LIF/VEGF expression and embryo implantation counts. In vitro, endometrial stromal cells (ESCs) were co-cultured with platelets, and mitochondrial transfer was tracked using MitoTracker®. Platelet mitochondrial respiration was inhibited with oligomycin/FCCP to assess functional contribution.
RESULTS: i-PRF released VEGF-A, TGF-β1, and PDGF-AB for up to 15 days (peak at 7 days), with a dense fibrin network entrapping abundant platelets. Ethanol injection significantly reduced endometrial thickness from 409.27 ± 55.86 μm to 104.48 ± 57.03 μm and decreased gland number from 22.4 ± 4.34 to 9.2 ± 3.77 (both p < 0.05).Administration of i-PRF reversed these pathological changes, restoring endometrial thickness to 464.11 ± 27.1 μm and gland count to 29.0 ± 9.41 (*p* < 0.05 vs. model). Immunohistochemical analysis revealed that i-PRF treatment increased the abundance of vimentin⁺,cytokeratin 18⁺ (CK-18⁺) and ki-67+ cells and enhanced the expression of leukemia inhibitory factor (LIF) and vascular endothelial growth factor (VEGF). Compared with the model group, the Ethanol + i‑PRF group exhibited a markedly higher embryo number (3.88 ± 3.91, P < 0.001); although this value was lower than that of the control group (5.00 ± 3.46), the difference did not reach statistical significance (P > 0.05). In vitro co-culture of endometrial stromal cells (ESCs) with platelets promoted ESC proliferation and VEGF secretion. Confocal microscopy confirmed the direct transfer of platelet mitochondria to ESCs. Inhibition of platelet mitochondrial respiration did not block ESC proliferation but significantly suppressed VEGF and vimentin expression (p < 0.05).
CONCLUSIONS: i-PRF effectively repairs thin endometrium in a rat model, and mitochondrial transfer from platelets to ESCs plays a key role in promoting endometrial regeneration. These findings support i-PRF as a promising therapy for TE.

Keywords:  Endometrial stromal cells; Injectable platelet-rich fibrin; Mitochondria; Platelets; Thin endometrium

DOI:  https://doi.org/10.1186/s13287-026-05181-4
Naunyn Schmiedebergs Arch Pharmacol. 2026 Oct 22.

Systemic mitochondrial injection protects against methanol-induced optic neuropathy through restoration of mitochondrial function and attenuation of oxidative stress.

Ahmad Salimi, Behrooz Elyasi, Hanieh Delavari, Hamed Karroubian, Elahe Zeynali, Salva Zaki, Mina Dehghanypoor, Zhaleh Jamali.

  Methanol poisoning can cause severe and irreversible optic neuropathy, for which effective neuroprotective strategies remain limited. Mitochondrial dysfunction is important contributors to methanol-induced neuronal injury. Therefore, this study evaluated whether systemic mitochondrial injection could attenuate methanol-induced optic nerve injury. Adult rats were randomly assigned to control, methanol, methanol + single mitochondrial injection, and methanol + double mitochondrial injection groups. Following methanol intoxication, freshly isolated functional mitochondria (250 µg/kg) were administered intravenously. Motor and visual functions were evaluated using the beam walking and visual cliff tests. Mitochondrial dysfunction was assessed by flow cytometric analysis of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Oxidative stress was assessed by measuring reduced glutathione (GSH) and malondialdehyde (MDA), and optic nerve histopathology was also examined. Methanol exposure impaired motor coordination and visual performance (P < 0.05) and was associated with increased ROS formation (P < 0.001), lipid peroxidation (P < 0.01), MMP collapse (P < 0.001), and GSH depletion (P < 0.05), accompanied by histopathological alterations in the optic nerve. Mitochondrial injection attenuated these changes (P < 0.05) and improved functional and histopathological outcomes. Overall, the double mitochondrial injection was associated with a relatively greater improvement than the single administration in some of the evaluated parameters. Systemic mitochondrial injection attenuated methanol-associated mitochondrial and oxidative disturbances and was accompanied by improved behavioral and histopathological outcomes in this experimental model. Obtained finding in the current study support further investigations of mitochondrial-based approaches as potential strategies for methanol-induced optic neuropathy, while additional works are required to establish their underlying mechanisms, durability, and translational potential.

Keywords:  Methanol intoxication; Mitochondrial dysfunction; Neuroprotection; Optic nerve injury; Oxidative stress

DOI:  https://doi.org/10.1007/s00210-026-06010-4
Int J Biol Sci. 2026 ;22(15): 8390-8407

Extracellular Mitochondrial Components as Emerging Biomarkers and Therapeutic Targets in Human Diseases.

Kuan-Hao Tsui, Emmanuel Naveen Raj, Andy P Tsai, Boyang Wang, Chen-Yueh Wen, Chia-Jung Li.

  Mitochondria serve as the bioenergetic hub of eukaryotic cells while simultaneously acting as a major source of cellular stress and toxicity. Classical mitochondrial quality control (MQC) has long been viewed as a lysosome-dependent process centered on mitophagy. However, aging is accompanied by progressive lysosomal dysfunction, limiting the efficiency of canonical mitochondrial clearance and contributing to mitochondrial accumulation and cellular deterioration. Emerging evidence suggests that under conditions of lysosomal overload and metabolic stress, cells engage alternative quality-control pathways by selectively exporting mitochondrial components into the extracellular environment through mitochondrial-derived vesicles (MDVs) and exophers. In this review, we integrate current findings to propose a unified framework of age-associated mitochondrial disposition and discuss how cells dynamically balance intracellular degradation with extracellular mitochondrial secretion. We further examine the molecular machinery underlying MDV and exopher biogenesis and evaluate their roles in reshaping intercellular metabolic communication. Particular emphasis is placed on their translational relevance in cancer and neurodegenerative disorders, where extracellular mitochondrial trafficking may contribute to disease progression, therapeutic resistance, and tissue remodeling. We also discuss the technical and analytical bottlenecks that currently constrain this field. Finally, we discuss the emerging potential of mitochondrial secretion pathways as diagnostic biomarkers and therapeutic targets for age-associated diseases.

Keywords:  intercellular transfer; lysosomes; mitochondrial-derived vesicles; mitophagy

DOI:  https://doi.org/10.7150/ijbs.140360
Proc Natl Acad Sci U S A. 2026 Oct 27. 123(43): e2613074123

Mitochondrial subpopulations promote cellular responses to changes in metabolic demand and signal transduction.

Tak Shun Fung, Elias Tzoc-Pacheco, Ruobing Cui, Shelby Brown, Simon Schwörer, Tullia Lindsten, Craig B Thompson, Keunwoo Ryu.

  When mammalian cells are under increased ATP demand, mitochondria segregate into two distinct subpopulations, one capable of oxidative phosphorylation (oxidative subpopulation) and another specialized in reductive synthesis of metabolic precursors (reductive subpopulation). Here we report that mitochondrial DNA (mtDNA) along with protein components of the mitochondrial nucleoid segregate to the oxidative subpopulation in response to increased ATP demand. This suggests that formation of the reductive mitochondrial subpopulation might serve to eliminate alternative uses of mitochondrial NAD(P)H when cells are under bioenergetic or nutrient stress. To examine this further, we studied mitochondria in cells exposed to low levels of glutamine. Mitochondria use glutaminase (GLS1) to maintain net glutamine uptake when cytosolic glutamine decreases, by converting glutamine to glutamate. The resulting glutamate can either be oxidized into α-ketoglutarate to enter the TCA cycle or utilized in the reductive synthesis of proline/ornithine. GLS1 can polymerize into hyperactive filaments in response to elevations in inorganic phosphate as might occur when ATP consumption exceeds production. However, when extracellular glutamine is reduced, GLS1 filaments segregated away from mtDNA, becoming colocalized with pyrroline-5-carboxylate synthase (P5CS) filaments in reductive mitochondria lacking ATP synthase markers. This cosegregation supported the ability of TGF-β signaling to enhance reductive proline/ornithine biosynthesis under low glutamine conditions despite compromising oxidative TCA cycle support from glutamine. The cosegregation of GLS1-P5CS filaments depended on continuing mitochondrial fission/fusion and occurred even in cells lacking mtDNA. Together, these data demonstrate that the reductive mitochondrial subpopulation is functional and under regulation by both metabolic demand and intercellular signal transduction.

Keywords:  GLS; P5CS; metabolism; mitochondria; mtDNA

DOI:  https://doi.org/10.1073/pnas.2613074123