bims-mitrat 2026-06-14 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–06–14
ten papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Mitochondrial transfer between tumor and immune cells: a nexus of metabolic adaptation and immune dysfunction.
Mitochondrial transfer reveals an organellar layer of cancer ecology.
Intercellular mitochondrial transfer in melanoma progression and therapeutic resistance: mechanisms and targeting potential.
Mitochondrion-targeted therapies for diabetic wound healing: from mechanism to therapeutic opportunity.
Mitochondrial Transfer from Glia to Neurons: A Novel Protective Mechanism Against Peripheral Neuropathy.
From energy provision to protein synthesis: Tunnelling nanotubes as mediators of intercellular metabolic cooperation in cancer.
Bioenergetic benefits and therapeutic potential of storable mitochondria.
Mitochondrial Transplantation-Mediated Restoration of Mitochondrial Function Alleviates Hepatic Ischemia-Reperfusion Injury in Mice.
Engineered Tan-CDs@AS-IV Nanosystem Orchestrates Mitochondrial Biogenesis and Intercellular Transfer to Restore Endothelial Function via PGC-1α and Cx43 Signaling Pathways.
Retrograde mitochondrial transport is required for mitochondrial biogenesis in zebrafish neurons.

Biomark Res. 2026 Jun 11.

Mitochondrial transfer between tumor and immune cells: a nexus of metabolic adaptation and immune dysfunction.

Jianqiang Yang, Yunqi Li, Soumya Vijaya Kumar, Nabil F Saba, Chloe Shay, Yong Teng.

  The tumor microenvironment (TME) is a dynamic and highly interactive ecosystem that fuels cancer progression through coordinated cellular crosstalk. Recent studies have uncovered intercellular mitochondrial transfer as a critical adaptive mechanism within this niche. Here, we synthesize current evidence supporting a paradigm in which mitochondria function as "shared organelles", whose bidirectional trafficking reshapes tumor and immune cell states. We discuss the mechanisms by which cancer cells acquire functional mitochondria from stromal compartments to enhance bioenergetic fitness, metabolic plasticity, and resistance to therapy. Conversely, we highlight the transfer of damaged or dysfunctional mitochondria from tumor cells to immune populations, a process that contributes to immune suppression and impaired anti-tumor responses. We further delineate the molecular and cellular networks regulating mitochondrial exchange, including tunneling nanotubes, extracellular vesicles, and cytoskeletal dynamics. Finally, we evaluate emerging therapeutic strategies aimed at disrupting mitochondrial trafficking and reprogramming TME metabolism. Collectively, this review positions mitochondrial transfer as a fundamental driver of tumor progression and a promising, yet underexplored, target for cancer therapy.

Keywords:  Antitumor therapy; Mitochondrial transfer; TME; Tumor immunity; Tumor-stromal cell interactions

DOI:  https://doi.org/10.1186/s40364-026-00955-7
Trends Cancer. 2026 Jun 11. pii: S2405-8033(26)00113-5. [Epub ahead of print]

Mitochondrial transfer reveals an organellar layer of cancer ecology.

Derick Okwan-Duodu, Bo Li, Edgar Engleman.

  Tumors are ecological systems shaped by continuous exchange with surrounding cells. The transfer of functional mitochondria, which reprograms malignant behavior, introduces a distinct layer to this ecology. Cancer evolution may proceed not solely through mutation and selection but also through the horizontal assimilation of organellar traits acquired from neighboring cells.

Keywords:  cancer hallmarks; metabolism; metastasis; mitochondrial transfer; organellar ecology

DOI:  https://doi.org/10.1016/j.trecan.2026.05.006
Front Oncol. 2026 ;16 1835726

Intercellular mitochondrial transfer in melanoma progression and therapeutic resistance: mechanisms and targeting potential.

Qingqing Yan, Tao Sun, Kang Chen, Hao Hu.

  Intercellular mitochondrial transfer has emerged as a novel mode of metabolic communication, enabling the exchange of functional mitochondria and their associated components between cells via tunneling nanotubes, extracellular vesicles, and direct cell-cell contact. Melanoma is a highly aggressive malignancy characterized by remarkable metabolic plasticity, in which disease progression and therapeutic resistance are closely linked to mitochondrial reprogramming. Accumulating evidence indicates that, under conditions of therapeutic pressure or metabolic impairment, melanoma cells can acquire exogenous mitochondria to restore oxidative phosphorylation (OXPHOS), maintain redox homeostasis, and enhance survival. This process contributes to resistance to targeted therapies, immune evasion, and increased invasive and metastatic potential. Conversely, in specific contexts, intercellular mitochondrial transfer may exert tumor-suppressive effects by enhancing the metabolic fitness of immune cells, activating innate immune signaling pathways, or inducing oxidative stress-mediated apoptosis. These findings underscore the context-dependent nature of its biological effects, which are governed by factors such as donor and recipient cell identity, mitochondrial integration status, and microenvironmental stress conditions. In this review, we systematically summarize the principal mechanisms of intercellular mitochondrial transfer and highlight its bidirectional roles in melanoma progression and therapeutic resistance. Furthermore, we propose a context-dependent regulatory framework and discuss potential intervention strategies. A deeper understanding of this process may provide new theoretical insights for integrating metabolic modulation with targeted and immunotherapeutic approaches in precision melanoma treatment.

Keywords:  immune regulation; intercellular mitochondrial transfer; melanoma; oxidative phosphorylation; therapeutic resistance; tumor microenvironment

DOI:  https://doi.org/10.3389/fonc.2026.1835726
Burns Trauma. 2026 ;14 tkag018

Mitochondrion-targeted therapies for diabetic wound healing: from mechanism to therapeutic opportunity.

Qipeng Wu, Fei Xiao, Han Wang, Yuan Xiong, Bobin Mi.

  Diabetic wounds are a major clinical challenge. They are driven by persistent hyperglycemia and chronic inflammation that synergistically disrupt mitochondrial homeostasis, manifesting as impaired bioenergetics, excessive reactive oxygen species (ROS) accumulation, and dysregulated mitochondrial quality control. Mitochondrial dysfunction critically undermines cellular proliferation, angiogenesis, and immunomodulation, which are essential for effective tissue repair. Intercellular mitochondrial transfer, mediated through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junctions (GJs), and cell fusion, has recently emerged as a biologically compelling endogenous rescue mechanism capable of restoring bioenergetic capacity and redox homeostasis in metabolically compromised recipient cells. In this review, we systematically examine the mechanistic basis of mitochondrial dysfunction in the diabetic wound microenvironment, critically evaluate the therapeutic potential of intercellular mitochondrial transfer, and propose an integrated mechanism-to-translational framework coupling transfer-based strategies with bioresponsive and mitochondrion-targeted biomaterials tailored to the pathological wound milieu. Furthermore, we identify key translational barriers-including insufficient protocol standardization, the absence of robust characterization criteria, and a lack of quantitative benchmarks for transfer efficacy-that must be addressed to advance these strategies toward clinical application, thereby offering a conceptual foundation and translational roadmap for mitochondrion-centered regenerative approaches in diabetic wound care.

Keywords:  Diabetic wounds; Mitochondrial dysfunction; Mitochondrial transfer; Oxidative stress; Therapeutic strategies

DOI:  https://doi.org/10.1093/burnst/tkag018
Neurosci Bull. 2026 Jun 09.

Mitochondrial Transfer from Glia to Neurons: A Novel Protective Mechanism Against Peripheral Neuropathy.

Xiao-Wen Meng, Yong-Jing Gao.

DOI: https://doi.org/10.1007/s12264-026-01659-6
FEBS Open Bio. 2026 Jun 08.

From energy provision to protein synthesis: Tunnelling nanotubes as mediators of intercellular metabolic cooperation in cancer.

Stanislava Martínková, Jan Trnka.

  Tunnelling nanotubes (TNTs) are thin intercellular membrane structures, which enable direct cytoplasmic communication between distant cells. Since their discovery two decades ago, TNTs have been identified in numerous physiological and pathological contexts. This includes cancer, where they contribute to metabolic cooperation, stress adaptation and treatment resistance. Here we summarise the current understanding of the structural and molecular characteristics of TNTs and their cargoes, including nucleic acids, proteins, organelles, pathogens and drugs. We also discuss the cytoskeletal and motor protein machinery underlying TNT biogenesis and cargo transport. Particular attention is also given to mitochondrial transfer and its role in intercellular metabolic cooperation or parasitism, mRNA transfer and its functional effects in recipient cells, and ribosome transfer which suggests intercellular proteosynthetic cooperation. Overall, while we have learned much about TNTs since their identification a little over 20 years ago, there remain significant questions and discoveries still to be made.

Keywords:  cancer; cytoskeleton; mRNA transfer; mitochondrial transfer; ribosomal transfer; tunnelling nanotubes

DOI:  https://doi.org/10.1002/2211-5463.70283
Biochem Biophys Res Commun. 2026 Jun 07. pii: S0006-291X(26)00883-1. [Epub ahead of print]828 154119

Bioenergetic benefits and therapeutic potential of storable mitochondria.

Takahiro Shibata, Yosif El-Darawish, Keiichi Sakakibara, Masae Takeda, Junko Hayashi, Yoshiharu Nitta, Yoshihiro Ohta, Yuma Yamada, Rick Tsai, Hisashi Ota, Masashi Suganuma.

Mitochondrial transplantation is an emerging therapeutic strategy for various diseases associated with mitochondria dysfunction; however, conventional isolation methods require fresh tissue due to the fragility of isolated mitochondria, limiting clinical application. We previously developed a novel isolation method to recover high-quality mitochondria (Mitochondria oRganelle Complex; MRC-Q) from cryopreserved cell stocks. In this study, we characterized the biological profiles of MRC-Q and investigated its intracellular behavior and metabolic impact on recipient cells. MRC-Q maintained exceptionally high structural integrity of both outer and inner membranes, respiratory capacity, and high catalase activity even after cryopreservation and thawing. When delivered to human fibroblasts and vascular endothelial cells, RFP-labeled MRC-Q was rapidly internalized as independent puncta without fusing with the endogenous mitochondrial network. MRC-Q treatment significantly enhanced cellular respiration and ATP levels, and upregulated the expression of electron transport chain components and mitochondrial transcription factor A (TFAM). Furthermore, MRC-Q conferred dose-dependent resistance to H2O2-induced oxidative stress. These results suggest that MRC-Q acts not only as a transient energy source but also as a biological catalyst that triggers endogenous mitochondrial biogenesis. Our findings demonstrated that MRC-Q is a scalable and potent candidate for next-generation mitochondrial replacement therapy.

DOI: https://doi.org/10.1016/j.bbrc.2026.154119
Transplant Proc. 2026 Jun 10. pii: S0041-1345(26)00280-0. [Epub ahead of print]

Mitochondrial Transplantation-Mediated Restoration of Mitochondrial Function Alleviates Hepatic Ischemia-Reperfusion Injury in Mice.

Yanling Hua, Zhiyu Wang, Minhao Wang, Yiqun Li, Li Li.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a major complication in liver surgery and transplantation, with mitochondrial dysfunction playing a central role. Mitochondrial transplantation has shown promise in other organ systems, but its effects and mechanisms in HIRI remain incompletely understood.
OBJECTIVE: This study aimed to investigate the protective effects of mitochondrial transplantation on HIRI and explore the underlying molecular mechanisms.
METHODS: HIRI was induced in male C57BL/6 mice by 60 minutes of partial hepatic ischemia followed by 3 hours of reperfusion. Autologous liver mitochondria (0.5 mg/kg) or vehicle were administered intravenously at the onset of reperfusion. In parallel, human THLE-2 hepatocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) with or without mitochondrial supplementation (50 μg/mL). Liver injury (serum ALT/AST, measured as mass concentrations by ELISA), histopathology, cytokine profiles (TNF-α, IL-6, IL-10), apoptosis (Bax, Bcl-2, Cleaved Caspase-3, Annexin V), mitochondrial function (membrane potential, ROS production), and cell viability were assessed.
RESULTS: Mitochondrial transplantation was associated with significantly reduced serum ALT and AST levels and attenuated histopathological liver damage in vivo (**p < .01). These changes correlated with a shift in cytokine balance, characterized by lower TNF-α and IL-6 and higher IL-10 levels, and with reduced expression of pro-apoptotic markers. In vitro, mitochondrial supplementation was associated with improved hepatocyte viability, reduced enzyme leakage, modulated cytokine secretion, and decreased apoptosis following OGD/R. These protective effects correlated with preserved mitochondrial membrane potential and reduced mitochondrial superoxide production.
CONCLUSIONS: Our findings suggest that mitochondrial transplantation is associated with mitigation of HIRI in a murine model and with improved mitochondrial parameters in stressed hepatocytes. These correlative data support the potential of this approach as a therapeutic strategy for HIRI.

DOI: https://doi.org/10.1016/j.transproceed.2026.04.031
Nanomaterials (Basel). 2026 Jun 04. pii: 698. [Epub ahead of print]16(11):

Engineered Tan-CDs@AS-IV Nanosystem Orchestrates Mitochondrial Biogenesis and Intercellular Transfer to Restore Endothelial Function via PGC-1α and Cx43 Signaling Pathways.

Haoran Wang, Xiaoyu Wang, Shuo Liu, Chunzhao Liu.

  Ischemic diseases are characterized by the functional collapse of endothelial cells (ECs) triggered by insufficient tissue perfusion. Given that mitochondria serve as the metabolic hub of ECs, their homeostatic imbalance, which is manifested by adenosine triphosphate (ATP) depletion, reactive oxygen species (ROS) bursts, and mitochondrial permeability transition pore opening, serves as the initiating factor driving impaired angiogenesis and tissue necrosis. In this study, we engineered an integrated nanosystem (Tan-CDs@AS-IV) by transforming Tanshinone into antioxidant carbon dots to encapsulate Astragaloside IV, achieving multi-level synergistic regulation of mitochondrial function. Our results demonstrate that Tan-CDs@AS-IV possesses superior structural stability and cellular internalization capabilities, significantly enhancing the migration and tubulogenesis of ECs under ischemic stress. Mechanistically, Tan-CDs@AS-IV effectively scavenges mitochondrial ROS and restores membrane potential and ATP production. Crucially, the nanosystem orchestrates mitochondrial biogenesis via peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) upregulation while simultaneously facilitating intercellular mitochondrial transfer through Connexin 43 (Cx43)-mediated gap junctions. This synergistic "endogenous amplification and intercellular replenishment" model establishes a robust mitochondrial quality control relay. By reconstructing cellular energy homeostasis, this study provides a novel nanoengineering strategy for the targeted therapy of ischemic diseases.

Keywords:  PGC-1α/Cx43 signaling; carbon dot-based nanosystem; endothelial function; intercellular mitochondrial transfer; mitochondrial biogenesis

DOI:  https://doi.org/10.3390/nano16110698
Nat Commun. 2026 Jun 12.

Retrograde mitochondrial transport is required for mitochondrial biogenesis in zebrafish neurons.

Angelica E Lang, Chris Stein, Roger Schultz, Catherine M Drerup.

To maintain a functional mitochondrial population in a long-lived cell like a neuron, mitochondria must be continuously replenished through the process of mitochondrial biogenesis. Because most mitochondrial proteins are nuclear encoded, mitochondrial biogenesis requires communication between mitochondria and the nucleus. This can be a challenge in a large, compartmentalized cell like a neuron in which a significant portion of the mitochondrial population is in neuronal compartments far from the nucleus. Using in vivo assessments of mitochondrial biogenesis in zebrafish neurons, we determined that mitochondrial transport between distal axonal compartments and the cell body is required for sustained mitochondrial biogenesis. Estrogen-related receptor transcriptional activation links transport with nuclear expression of mitochondrial genes. Together, our data support a role for retrograde feedback between axonal mitochondria and the nucleus for regulation of mitochondrial biogenesis in neurons.

DOI: https://doi.org/10.1038/s41467-026-74127-4