bims-mitrat 2026-04-12 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–04–12
twelve papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Mitochondrial Transfer to Endothelial Cells: Mechanisms, Evidence, and Therapeutic Potential.
Mitochondrial transplantation for osteoarthritis: from molecular mechanisms to clinical translation.
Clotting the Gap Between Mitochondria-Mediated Immunity and Mitochondrial Transfer.
Mitochondria Transplantation Preserves Retinal Ganglion Cells and Promotes CNS Axonal Regeneration.
Mitochondrial transplantation in lung diseases: From mechanisms to application prospects.
Mitochondrial Transfer: From Bench to Bedside.
Mitochondria transfer in tissue homeostasis and diseases.
Intercellular Mitochondrial Transfer: Implications in Cardiovascular Health.
Mitochondrial transfer in acute myeloid leukaemia and multiple myeloma: Mechanisms, consequences and potential therapeutic opportunities.
Extracellular biogenic nanoscale mitochondria reprogram the wound microenvironment via ROS scavenging independent of cellular uptake.
Two Routes for Removing Unhealthy Mitochondria: Degradation and Secretion.
Mitochondria-Derived Vesicles and Mitochondrial Extracellular Vesicles in Health and Cardiovascular Disease.

Circ Res. 2026 Apr 10. 138(8): e326982

Mitochondrial Transfer to Endothelial Cells: Mechanisms, Evidence, and Therapeutic Potential.

Gwang-Bum Im, Juan M Melero-Martin.

  Mitochondria are increasingly recognized as central regulators of vascular health, shaping endothelial cell function through roles that extend far beyond energy production. In addition to coordinating redox balance, calcium dynamics, and biosynthetic support, recent studies have revealed that mitochondria participate in intercellular communication, with evidence of transfer events emerging in vascular contexts. Parallel efforts have advanced the deliberate delivery of exogenous mitochondria from preclinical proof-of-principle studies to first-in-human trials, demonstrating that freshly isolated organelles can be harvested and administered in real-time to critically ill patients with favorable early outcomes. The mechanisms underlying these benefits remain incompletely defined, and strategies for efficient and scalable delivery are still emerging. In this review, we prioritize recent evidence linking mitochondrial function to endothelial cell physiology, highlight the nascent but growing field of mitochondrial transfer in the vasculature, and examine how mitochondrial transplantation is evolving from experimental concept to clinical translation. Together, these advances point to new therapeutic avenues for preserving vascular integrity and treating disease.

Keywords:  cell communication; endothelial cells; mitochondria; regenerative medicine; therapeutics

DOI:  https://doi.org/10.1161/CIRCRESAHA.125.326982
Front Immunol. 2026 ;17 1716906

Mitochondrial transplantation for osteoarthritis: from molecular mechanisms to clinical translation.

Ying Liu, Yang Liu, Na Zhang, Haizhuan An, Liangyu Mi, Yanan Gao, Ke Xu.

  Osteoarthritis (OA) is the most prevalent chronic degenerative joint disorder worldwide, characterized by progressive cartilage degradation, subchondral bone remodeling, synovial inflammation, and impaired mobility. Growing evidence has established mitochondrial dysfunction-including impaired oxidative phosphorylation (OXPHOS), excessive reactive oxygen species (ROS) generation, disrupted mitochondrial dynamics, and dysregulated mitophagy-as an early and pivotal driver of OA pathogenesis. These bioenergetic failures not only disrupt chondrocyte metabolism but also amplify inflammation, matrix degradation, and cell death. In recent years, mitochondrial transplantation has emerged as a revolutionary therapeutic paradigm, aiming to restore cellular homeostasis by delivering functional mitochondria into damaged chondrocytes. This review systematically summarizes the molecular mechanisms of mitochondrial dysfunction in OA and highlights three major therapeutic strategies: (1) cell-based approaches, particularly mesenchymal stem cell (MSC)-mediated mitochondrial transfer via tunneling nanotubes (TNTs) or extracellular vesicles (EVs); (2) cell-free approaches, utilizing purified mitochondria or MitoEVs for direct transplantation; and (3) engineered mitochondrial transplantation, integrating bioengineering, nanotechnology, and genetic modification to enhance mitochondrial quality, delivery efficiency, and therapeutic persistence. We further discuss opportunities and challenges in clinical translation, including standardization of mitochondrial preparation, optimization of delivery systems, immunological safety, and regulatory classification. Collectively, mitochondrial transplantation represents a disruptive strategy that directly addresses the bioenergetic collapse of chondrocytes and offers a promising avenue for disease-modifying therapy in OA. Future advances in mechanistic elucidation, technological optimization, and multicenter clinical trials will be crucial to transform "mitochondrial medicine" from experimental concept to clinical reality.

Keywords:  extracellular vesicles; mitochondrial dysfunction; mitochondrial transplantation; mitophagy; osteoarthritis; oxidative phosphorylation; regenerative medicine; stem cells

DOI:  https://doi.org/10.3389/fimmu.2026.1716906
Circ Res. 2026 Apr 10. 138(8): e326987

Clotting the Gap Between Mitochondria-Mediated Immunity and Mitochondrial Transfer.

Florian Tupin, Jorge A Gonzalez-Chapa, Jay H Chung, Christian Lood, Eric Boilard.

  Mitochondria are organelles that orchestrate numerous cell functions in addition to providing energy. During viral infection or in case of defects in mitochondrial replication, an intricate mechanism of self-destruction is engaged through the formation of mitochondrial pores. This leads to the release of mitochondrial DNA into the cytoplasm, where it triggers innate immune responses. Platelets constitute the principal source of circulating mitochondria, and increasing evidence demonstrates that they actively release mitochondria, some of which are enclosed within extracellular vesicles. This process is enhanced in autoimmune conditions, occurs in platelet storage, and has been linked to adverse reactions after platelet transfusion. Extracellular mitochondria act as carriers of damage-associated molecular patterns and are targets of antibodies in various pathologies, including antiphospholipid syndrome and cardiomyopathies. Moreover, elevated levels of antimitochondria antibodies have also been associated with increased mortality and cardiovascular risk in systemic lupus erythematosus. Mitochondrial transplantation, a process by which defective mitochondria in a tissue or organ may be replaced by healthy mitochondria, is receiving growing therapeutic interest. Thus, understanding how extracellular mitochondria interact with the immune system is increasingly important. This review summarizes current knowledge on the multifaceted roles of mitochondria in immunity, with a particular focus on platelets and platelet-derived mitochondria as a key biological context.

Keywords:  DNA, mitochondrial; autoantibodies; immunity, adaptive; immunity, innate; mitochondria

DOI:  https://doi.org/10.1161/CIRCRESAHA.125.326987
Free Radic Biol Med. 2026 Apr 06. pii: S0891-5849(26)00266-2. [Epub ahead of print]

Mitochondria Transplantation Preserves Retinal Ganglion Cells and Promotes CNS Axonal Regeneration.

Ajay Ashok, Kin-Sang Cho, Wai Lydia Tai, Lu Huang, Hio Tong Kam, Suman Chaudhary, Karen Chang, Sarita Pooranawattanakul, Julie Chen, Anton Lennikov, Dong Feng Chen.

  Mitochondrial dysfunction is a central driver of retinal ganglion cell (RGC) loss in glaucoma and other forms of optic neuropathies, leading to irreversible blindness. Here, we demonstrate that replenishing the mitochondrial pool through exogenous mitochondrial transplantation ("mitotherapy") in adult mice not only preserves neuronal survival but also promotes regenerative competence in the central nervous system (CNS). In aging or injured RGCs, we identified profound deficits in mitochondrial biogenesis, fission-fusion balance, and mitophagy. Transplantation of functional mitochondria in in vitro models of trophic deprivation and glutamate excitotoxicity restored mitochondrial homeostasis, improved energy production, reduced reactive oxygen species, enhanced RGC survival, and drove robust neurite outgrowth, with transplanted mitochondria actively trafficking to growth cones. This effect was dampened following inhibition of mitochondrial fusion indicating a pivotal role of fusion-dependent functional integration of exogenous mitochondria. Strikingly, intravitreal delivery of mitochondria in an optic nerve crush model of adult mice enabled their integration into RGCs, improved survival and electrophysiological responses, and supported axonal regeneration across the lesion site. These findings indicate that mitochondrial transplantation strategy rescues bioenergetic failure and supports a pro-regenerative activity of neurons, highlighting the potential of mitotherapy as a transformative approach for neurodegenerative eye diseases and CNS injuries.

Keywords:  Mitochondrial transplantation; PC12 cells; SH-SY5Y cells; nerve regeneration; neuroprotection; optic nerve crush; retinal ganglion cells

DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.03.069
Genes Dis. 2026 Jul;13(4): 101856

Mitochondrial transplantation in lung diseases: From mechanisms to application prospects.

Haoneng Wu, Qiuran Zhao, Ying Zhao, Jinguang Bai, Junxi Pan, Songling Huang.

  Mitochondria are double-membrane organelles in eukaryotic cells, which play an important role in energy metabolism, cell cycle and apoptosis. Therefore, mitochondrial abnormalities can affect various physiological and pathological processes. Extensive research over a long period of time has shown that mitochondrial dysfunction is considered a hallmark of several diseases, including cardiovascular diseases, neurodegenerative diseases, respiratory diseases, and even cancer. Mitochondrial transplantation has emerged in recent years as a novel approach for treating mitochondria-related diseases. This therapy involves transferring viable, functionally intact mitochondria into cells or tissues, either directly or indirectly, to replace dysfunctional mitochondria and restore mitochondrial function, thereby achieving therapeutic goals. Research has indicated that mitochondrial transplantation can alleviate the progression of lung diseases and improve disease outcomes. In this review, we explore the mechanisms underlying mitochondrial dysfunction in lung disease and the potential application of mitochondrial transplantation in the treatment of lung disease.

Keywords:  Lung disease; Mitochondrial dysfunction; Mitochondrial transplantation; Oxidative stress; Respiratory system

DOI:  https://doi.org/10.1016/j.gendis.2025.101856
Circ Res. 2026 Apr 10. 138(8): e326984

Mitochondrial Transfer: From Bench to Bedside.

Gentaro Ikeda, Jiwen Li, Alyssa Wang, Amogha Medha Paleru, Phillip C Yang.

  Intercellular mitochondrial transfer has emerged as a fundamental mechanism of tissue adaptation and repair in the cardiovascular system, with major implications for cardiovascular, neurological, metabolic, and inflammatory diseases. Once thought to be static, mitochondria are now recognized as mobile organelles that move between cells via tunneling nanotubes, extracellular vesicles, and free mitochondria. These pathways support 2 complementary axes of mitochondrial communication: Rescue by Replenish, in which healthy mitochondria or mitochondrial components restore bioenergetics and stress resistance in recipient cells, and Relief by Release, in which damaged mitochondria are exported for degradation to preserve homeostasis and limit inflammation. We summarize the molecular machinery governing tunneling nanotube formation, mitochondria-derived vesicle biogenesis, extracellular vesicle sorting, and free mitochondrial release and uptake, and discuss how these processes shape organ function. Building on these mechanistic insights, we outline 4 translational strategies: (1) cell-based therapies that donate healthy mitochondria or scavenge damaged ones; cell-free approaches using (2) mitochondria-containing extracellular vesicles or (3) purified mitochondria; (4) pharmacological, nutritional, and lifestyle interventions that augment endogenous mitochondrial turnover and intercellular exchange. Finally, we discuss key barriers to clinical translation, including inflammatory and oncogenic risks, mitonuclear incompatibility, incomplete understanding of the fate and durability of transferred mitochondria, and the lack of standardized manufacturing, potency assays, and long-term storage methods. Continued integration of mechanistic biology with bioengineering and regulatory science will be essential to safely move mitochondrial transfer-based therapies from bench to bedside in cardiovascular medicine.

Keywords:  cell communication; energy metabolism; extracellular vesicles; homeostasis; inflammation; mitochondria; nanotubes

DOI:  https://doi.org/10.1161/CIRCRESAHA.125.326984
Int J Biol Sci. 2026 ;22(6): 3144-3173

Mitochondria transfer in tissue homeostasis and diseases.

Lei Qin, Donghao Gan, Zecai Chen, Zhen Xu, Mingyue Wu, Bimin Gao, Yufeng Long, Xihong Mou, Wenqing Li, Weihong Yi, Guozhi Xiao.

  Mitochondria serve as the essential powerhouse for virtually all eukaryotic cells and have been implicated in other crucial functions in both physiological and disease contexts. As cytoplasmic organelles, mitochondria are segregated and transported from parent to daughter cells during division or differentiation, a process known as vertical mitochondria transfer (VMT). A growing body of literature indicates that various cell types can export mitochondria for delivery to developmentally unrelated cell types without division, a process termed horizontal mitochondria transfer (HMT). In this review, we summarize current understanding of the modes of mitochondria transfer and illustrate the phenomenon of HMT across different tissue backgrounds, including the immune, cardiovascular, respiratory, hepatic, renal, musculoskeletal, adipose, and reproductive systems. Moreover, updated applications and functions of mitochondria transfer are discussed. Additionally, we also highlight the therapeutic potential of mitochondria transfer in current preclinical and clinical trials for inherited mitochondrial diseases, cancer, wound healing, and injuries of the respiratory and central nervous systems.

Keywords:  extracellular vesicles (EVs); gap junctions (GJs); horizontal mitochondria transfer; intercellular mitochondria transfer; tunneling nanotubes (TNT); vertical mitochondria transfer

DOI:  https://doi.org/10.7150/ijbs.129709
Circ Res. 2026 Apr 10. 138(8): e326986

Intercellular Mitochondrial Transfer: Implications in Cardiovascular Health.

Yajun Wang, Rong Tian.

  Mitochondria are important organelles for metabolic homeostasis, cell fate, and survival. Emerging evidence suggests that mitochondria are not confined to the cells. Intercellular mitochondrial transfer (IMT) is increasingly recognized between a variety of cells, including major cell types in the cardiovascular system. Observations made by coculture systems, genetic lineage-tracing approaches, and animal models indicate that mitochondria can be transferred between cardiomyocytes, fibroblasts, endothelial cells, vascular smooth muscle cells, cardiac macrophages, and mesenchymal stromal cells. IMT has also been reported between a remote organ, for example, adipose tissue, and the heart, suggesting that mitochondrial trafficking can mediate communications not only between individual cells but also across organs. Two principal modes of IMT are reported. One involves directed, contact-dependent trafficking of mitochondria through membranous contacts or nanotubes. The other relies on the release of mitochondria, either packaged in membrane-bound vesicles or as free mitochondria, into the extracellular space followed by import into the acceptor cells. Consequences of IMT can be beneficial or detrimental depending on the cell type and the conditions under which the IMT occurs. Mechanisms underlying the transfer or its consequences are not fully understood, however. The role of IMT in cardiovascular health is, therefore, interpreted with certain assumptions. In this review, we first summarize the evidence of IMT in the cardiovascular system and the observed functional outcome. We then aim to identify the knowledge gaps and critical questions to be addressed, followed by a discussion of challenges and opportunities to advance the field.

Keywords:  cardiovascular system; cell communication; extracellular vesicles; mitochondria; myocytes, cardiac

DOI:  https://doi.org/10.1161/CIRCRESAHA.125.326986
FEBS J. 2026 Apr 10.

Mitochondrial transfer in acute myeloid leukaemia and multiple myeloma: Mechanisms, consequences and potential therapeutic opportunities.

Ebubechukwu Nwarunma, Mark T S Williams.

  Haematological malignancies, such as acute myeloid leukaemia (AML) and multiple myeloma (MM), which develop from malignant transformations within the bone marrow, represent the most critical unmet needs in the haemato-oncology field. Sub-optimal clinical outcomes in patients with AML and MM are often driven by resistance to chemotherapy. It is well established that cells within the bone marrow microenvironment (BMME) support the proliferation and survival of these blood cancer cells. One of the mechanisms by which these BMME-resident cells support the malignant cells is through horizontal mitochondrial transfer (HMT), a mechanism well documented as occurring under steady-state conditions as well as in many cancers. Recent research implicates mitochondrial transfer in BMME-driven chemoresistance in AML and MM. In this review, we critically analyse current understanding of the role of HMT in supporting the survival and proliferation of AML and MM cells, as well as driving resistance to cytotoxic effects of chemotherapy. We further elucidate various mechanisms, molecular triggers, functional consequences, and therapeutic implications for HMT in AML and MM. Our review also highlights unanswered questions within the HMT field and provides a theoretical basis for further study, giving direction on what is important in translating this knowledge into effective future therapeutic strategies.

Keywords:  Horizontal mitochondrial transfer (HMT); Multiple myeloma (MM); acute myeloid leukaemia (AML); bone marrow microenvironment (BMME); chemoresistance

DOI:  https://doi.org/10.1111/febs.70544
Mater Today Bio. 2026 Jun;38 103023

Extracellular biogenic nanoscale mitochondria reprogram the wound microenvironment via ROS scavenging independent of cellular uptake.

Fang Lin, Jing Liu, Yue Ding, Kexin Ma, Qingshu Meng, Xiaohui Zhou, Qingliu Zhang, Hao Hu, Zhongmin Liu, Xiaoting Liang.

  Mitochondria are nanoscale organelles essential for cellular metabolism and redox regulation, making them a compelling target for regenerative therapeutics. Analysis of wound-edge tissues from pediatric patients with chronic non-healing ulcers revealed marked metabolic insufficiency and impaired regenerative signaling, underscoring an unmet clinical need for mitochondrial-based interventions. Here, we show that topically applied mesenchymal stem cell-derived mitochondria (MSC-mt), functioning as naturally derived nanoscale organelles, markedly accelerate wound closure in a murine full-thickness skin injury model. MSC-mt enhanced angiogenesis, collagen deposition, and fibroblast survival while reducing oxidative stress and apoptosis. Mechanistically, their cytoprotective effects occur primarily through extracellular scavenging of reactive oxygen species (ROS), independent of cellular internalization. Excessive immobilization of MSC-mt within a thermosensitive hydrogel compromised their efficacy, emphasizing the importance of mitochondrial mobility and microenvironmental access. Under high oxidative stress, internalized MSC-mt activated PINK1-Parkin-mediated mitophagy, indicating a context-dependent intracellular quality-control response. These findings position MSC-mt as a cell-free, organelle-level nano-therapeutic that operates through a dual extracellular-intracellular mechanism and emphasize the importance of delivery strategies that preserve mitochondrial functionality and spatial freedom.

Keywords:  Mesenchymal stem cells; Mitochondrial transplantation; Mitophagy; ROS scavenging; Wound healing

DOI:  https://doi.org/10.1016/j.mtbio.2026.103023
Circ Res. 2026 Apr 10. 138(8): e326985

Two Routes for Removing Unhealthy Mitochondria: Degradation and Secretion.

Xi Fang, Åsa B Gustafsson.

  Mitochondria are highly dynamic, double-membraned organelles that generate the majority of ATP in cardiomyocytes while supporting cellular homeostasis and signal transduction. Accumulation of dysfunctional mitochondria can promote cardiomyocyte loss, impair contractile function, and ultimately lead to myocardial damage. To preserve mitochondrial integrity, cardiomyocytes rely on multilayered quality control mechanisms to remove defective mitochondria. Two major routes have emerged for this process: degradation, primarily via autophagy, and secretion via extracellular vesicles. This review summarizes the mechanisms of mitochondrial degradation and secretion in the heart and highlights their contributions to cardiac disease progression and potential as therapeutic targets.

Keywords:  extracellular vesicles; homeostasis; mitochondria; mitophagy; myocytes, cardiac

DOI:  https://doi.org/10.1161/CIRCRESAHA.125.326985
Circ Res. 2026 Apr 10. 138(8): e327357

Mitochondria-Derived Vesicles and Mitochondrial Extracellular Vesicles in Health and Cardiovascular Disease.

Erjola Rapushi, Anubhav Aryal, Tianyuan Yang, Zhixin Li, Xiaohong Wang, Guo-Chang Fan.

  Mitochondria-derived vesicles (MDVs) and mitochondrial extracellular vesicles (mitoEVs) represent 2 related extensions of mitochondrial dynamics that link organelle maintenance to communication within and between cells. MDVs are small vesicles that bud directly from mitochondria, selectively packaging components of the outer membrane, inner membrane, or matrix. They serve as a localized quality control mechanism that removes oxidized or damaged material without engaging the entire mitophagic machinery. After budding, MDVs typically enter the endolysosomal pathway, where they can fuse with late endosomes or lysosomes for cargo degradation. A subset of MDVs also targets other organelles, particularly peroxisomes, contributing to organelle crosstalk, lipid metabolism, and redox balance. By contrast, mitoEVs released into the extracellular space contain intact functional mitochondria, mitochondrial contents (proteins, DNAs/RNAs, lipids, and so on), and nonmitochondrial cargo (ie, mRNAs, noncoding RNAs, and so on), which can be transferred to recipient cells and subsequently induce either pathogenic or beneficial outcomes. Therefore, mitoEVs have been implicated in metabolic cooperation, immune regulation, tissue remodeling, and aging. Accordingly, this review summarizes recent progress on the diverse mechanisms for the biogenesis of MDVs and mitoEVs, as well as available protocols for their isolation. The roles of MDVs and mitoEVs in mediating mitochondrial quality/quantity control and multiple layers of crosstalk between intracellular organelles and different cell types in health and disease are highlighted. Last, mitoEV-mediated pathogenic effects and therapeutic potential in cardiovascular disease are also discussed.

Keywords:  cardiovascular diseases; extracellular vesicles; lipid metabolism; mitochondria; reactive oxygen species

DOI:  https://doi.org/10.1161/CIRCRESAHA.125.327357