bims-mitrat 2026-07-12 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–07–12
nine papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Intercellular Mitochondrial Transfer and Mitochondrial Transplantation in Cardiovascular Disease.
Restoring the powerhouse: mitochondrial transplantation in regenerative medicine and cancer therapy.
Immune regulation in mitochondrial transfer: knowledge structure and emerging trends from a bibliometric perspective.
Mitochondrial transplantation reverses the senescence phenotype of SH-SY5Y cells.
Intercellular mitochondrial transfer and trans-mitophagy in response to protein import dysfunction.
Droplet Microfluidics-Enabled Mitochondrial Transfer from Young to Senescent MSCs to Ameliorate Cellular Senescence.
Exogenous mitochondrial transplantation attenuates oxidative stress-driven retinal degeneration in a sodium iodate - induced mouse model.
Plant-derived mitochondria mitigate aging-related neurodegeneration by reprogramming microglial mitochondrial energy metabolism.
A microfluidic platform for isolating functional mitochondria and restoring bioenergetic activity in hypoxia-injured cardiomyocytes.

Can J Cardiol. 2026 Jul 07. pii: S0828-282X(26)00654-9. [Epub ahead of print]

Intercellular Mitochondrial Transfer and Mitochondrial Transplantation in Cardiovascular Disease.

Fatemeh Farhid, Farshad Heydari, Michael R Hamblin, Saman Masoudifar, Amirhossein Sahebkar, Jalal Naghinezhad.

  Mitochondria have traditionally been regarded as intracellular powerhouses; however, they are now recognized as dynamic intercellular signaling organelles capable of moving between cells to coordinate tissue adaptation and repair. This Review examines the emergence of mitochondria transfer as a fundamental mechanism of cardiovascular communication, integrating current evidence for the exchange of intact mitochondria, mitochondrial DNA, and mitochondrial components among cardiomyocytes, endothelial cells, vascular smooth muscle cells, fibroblasts, and immune cells. We discuss the major routes of mitochondria transfer, including tunneling nanotubes, extracellular vesicles, gap junction-associated pathways, and extracellular mitochondrial release, together with the molecular machinery governing mitochondrial trafficking, such as MIRO proteins, TRAK adaptors, and cytoskeletal motor complexes. By reshaping cellular bioenergetics, redox homeostasis, metabolic signaling, and innate immune responses, transferred mitochondria exert profound effects on cardiovascular homeostasis and disease, influencing ischemia-reperfusion injury, heart failure, vascular remodeling, and inflammatory vascular disorders. We further evaluate recent advances in mitochondria transplantation, engineered mitochondrial donor platforms, and emerging imaging technologies that enable tracking of mitochondrial fate in vivo. Finally, we propose an integrated mechanistic framework in which the biological consequences of mitochondria transfer and mitochondria transplantation are determined by donor-recipient compatibility, mitochondrial quality, and the surrounding microenvironment, thereby explaining their context-dependent protective, maladaptive, and immunomodulatory effects. By identifying critical gaps in molecular mechanisms, methodological standardization, and clinical validation, this Review outlines a roadmap for translating mitochondria-based therapeutic strategies into precision cardiovascular medicine.

Keywords:  Bioenergetics; Cardiovascular disease; Extracellular vesicles; Heart failure; Mitochondrial transfer; Mitochondrial transplantation; Regenerative cardiology

DOI:  https://doi.org/10.1016/j.cjca.2026.06.032
Nanoscale. 2026 Jul 08.

Restoring the powerhouse: mitochondrial transplantation in regenerative medicine and cancer therapy.

Ngoc-Tri Tran, Hsiu-Ching Liu, Der-Yang Cho, Ming-You Shie, Shang-Hsiu Hu.

Mitochondrial dysfunction acts as a central contributor to diverse pathologies, ranging from neurodegenerative disorders to cancer, yet traditional pharmacotherapy often fails to restore organelle bioenergetics. Building on the discovery of natural intercellular mitochondrial transfer, Mitochondrial Transplantation (MtT) has emerged as a groundbreaking strategy to replace damaged organelles with healthy exogenous mitochondria. The present review synthesizes the recent progress in MtT, highlighting the intervention's dual therapeutic role: restoring metabolic homeostasis in regenerative medicine and reversing metabolic reprogramming to sensitize tumors in oncology. The text critically assesses current isolation techniques and innovative delivery strategies designed to overcome stability and uptake challenges. By evaluating biological mechanisms and translational barriers of "mitotherapy", the article provides a comprehensive theoretical foundation for advancing precision organelle-centered medicine.

DOI: https://doi.org/10.1039/d6nr00488a
Front Immunol. 2026 ;17 1850600

Immune regulation in mitochondrial transfer: knowledge structure and emerging trends from a bibliometric perspective.

Qiyu He, Zhimin Tan, Juan Xu, Tianhong Wang, Qian Li, Xiaoqiang Li.

   Background: Mitochondrial transfer has emerged as an important form of intercellular communication with growing relevance to immune regulation, inflammation, tissue repair, and tumor immunity. However, the knowledge structure, developmental trajectory, and emerging hotspots of this field remain unclear.
Methods: We conducted a bibliometric analysis of studies on mitochondrial transfer and immune regulation published between 2016 and 2025. Publications were retrieved from PubMed, Embase, the Cochrane Library, Scopus, and Web of Science, and analyzed using bibliometrix in R and CiteSpace. Annual publication trends, contributions of countries, institutions, authors, and journals, as well as keyword co-occurrence, clustering, burst detection, and co-citation patterns were evaluated.
Results: A total of 967 publications were included. Annual publication output increased steadily, with faster growth after 2020. China and the United States were the leading contributors and occupied central positions in international collaboration networks. Keyword and co-citation analyses showed that early studies mainly focused on mitochondrial DNA-associated inflammatory sensing, innate immunity, and inflammatory injury, whereas recent studies increasingly emphasized intercellular mitochondrial transfer, mitochondrial transplantation, T-cell function, tumor-associated macrophages, cancer immunotherapy, metabolic rewiring, and autophagy-associated mitochondrial quality control. Mitochondrial transplantation and tunneling nanotube were among the most prominent burst terms. Co-citation analysis identified major knowledge domains related to mitochondrial danger signaling, intercellular transfer mechanisms, mesenchymal stem cell-mediated immune regulation, tumor immunity, and translational applications.
Conclusion: Bibliometric mapping shows a clear shift from mitochondrial danger signaling toward intercellular transfer and immune-cell metabolic remodeling. Current evidence suggests that immune outcomes are shaped by mitochondrial source, transfer route, recipient-cell state, and disease context. More source-defined and context-specific studies are needed to clarify the therapeutic potential of mitochondrial transfer.

Keywords:  bibliometric analysis; immune regulation; immunometabolism; mitochondrial transfer; mitochondrial transplantation

DOI:  https://doi.org/10.3389/fimmu.2026.1850600
Mol Ther Adv. 2026 Sep 10. 34(3): 201788

Mitochondrial transplantation reverses the senescence phenotype of SH-SY5Y cells.

Liqun Xu, Yilang Wu, Wanfei Wu, Xiao Li, Ronghao Deng, Haibao Zhu, Aihua Mao, Pingnan Sun, Xin Zhang, Wencan Xu, Chi-Ju Wei.

  Fusogenic plasma membrane vesicles (PMVs) were engineered as carriers for mitochondrial delivery into senescent SH-SY5Y cells, a human neuroblastoma cell line widely used as an in vitro model for neurodegenerative diseases. Mitochondrial transfer was achieved via cell fusion mediated by the fusogenic vesicular stomatitis virus glycoprotein G. After mitochondrial transplantation, senescent SH-SY5Y cells exhibited marked phenotypic reversal, accompanied by restoration of glucose metabolism, ATP production, lactate levels, and mitochondrial respiratory activity to near-normal levels. In addition, mitochondrial transplantation regulated the senescence-associated secretory phenotype and associated inflammatory signaling pathways, while significantly enhancing antiapoptotic activity. Single-nucleotide polymorphism tracing of mitochondrial DNA confirmed the stable persistence of transplanted mitochondria within recipient cells, which was associated with recovery of normal mitochondrial morphology, function, and biogenesis. Notably, autophagic activity decreased after mitochondrial transplantation. Finally, alpha-synuclein expression was reduced, whereas dopamine production and the activities of enzymes involved in dopamine synthesis were increased after mitochondrial transplantation. The results demonstrated that mitochondrial transplantation can effectively reverse the senescence phenotype of SH-SY5Y cells, suggesting that mitochondrial transplantation may represent a promising therapeutic strategy for neurodegenerative disorders such as Parkinson disease.

Keywords:  PMVs; Parkinson disease; SH-SY5Y cells; SNP analysis; autophagy; cellular senescence; mitochondria transplantation; plasma membrane vesicles; single-nucleotide polymorphism analysis

DOI:  https://doi.org/10.1016/j.omta.2026.201788
J Cell Biol. 2026 Sep 07. pii: e202511211. [Epub ahead of print]225(9):

Intercellular mitochondrial transfer and trans-mitophagy in response to protein import dysfunction.

Emily Glover, Beth Wiseman, Celyn Dugdale, Charlie Humphery, Lorena Sueiro Ballesteros, Lorna Hodgson, Kevin Wilkinson, Ian Collinson.

Mitochondrial protein import is critical for organelle biogenesis, maintenance, and regeneration-essential for cellular homeostasis. Import dysfunction compromises cellular energy supplies, which is damaging to cells, particularly those with high energetic demands like neurons. Previously, we have shown that import failure is rescued by intercellular mitochondrial transfer (IMT) via tunnelling nanotubes (TNTs) however, the fate of the transferred mitochondria and the mechanistic basis for rescue were unresolved. Here, we show that bidirectional mitochondrial trafficking between cells harboring import-defective and import-competent mitochondria is distinct in terms of their regulation and ensuing consequences. Transferred import-defective mitochondria are highly fragmented and destined for canonical lysosomal degradation. In contrast, reactive oxygen species (ROS)-producing mitochondria at the periphery of cells with import-competent mitochondria are transferred into neighboring cells undergoing import failure. These new arrivals then accumulate within previously uncharacterized "mitochondrial degradation bodies" (MDBs). We speculate that the cooperation of these distinct cases of TNT-mediated conventional and noncanonical "trans-mitophagy" instigates mitochondrial regeneration, and thereby rescues mitochondrial function.

DOI: https://doi.org/10.1083/jcb.202511211
ACS Appl Mater Interfaces. 2026 Jul 06.

Droplet Microfluidics-Enabled Mitochondrial Transfer from Young to Senescent MSCs to Ameliorate Cellular Senescence.

Zhen Liu, Meijun Wang, Jiayu Sun, Wayne Y W Lee, Ho Yin Tsang, Kwan Ting Chow, Dong Sun.

  Mesenchymal stem cells (MSCs) are widely used for tissue repair and regeneration, but prolonged in vitro expansion induces senescence and limits their therapeutic efficacy. Given the key role of mitochondria in cellular senescence and metabolic regulation, mitochondrial transfer may offer a promising strategy for ameliorating senescence-associated phenotypes. However, conventional mitochondrial transfer methods, such as coculture and microinjection, are limited by poor quantitative control, low throughput, and potential cell damage. Here, an inertial-focusing-assisted droplet microfluidic platform was developed for high-throughput, high-efficiency, and quantitative control of mitochondrial transfer at the single-cell level. The platform achieved 29.2% single-cell droplets and 1.3% multicell droplets, with a transfer efficiency of up to 56% at a droplet generation rate exceeding 4000 Hz. Using this platform, the transfer of 19 mitochondria from young adipose-derived MSCs (ADSCs) to senescent ADSCs enhanced proliferation capacity and metabolic activities, reduced senescence-associated markers, and transformed the senescent phenotype into a young MSC-like phenotype. The developed technique provides a cell therapy strategy for mitochondrial-related diseases.

Keywords:  cell therapy; cellular senescence; droplet microfluidics; mesenchymal stem cells; mitochondrial transfer; single-cell level

DOI:  https://doi.org/10.1021/acsami.6c05873
Neurobiol Aging. 2026 Jul 06. pii: S0197-4580(26)00123-5. [Epub ahead of print]168 1-13

Exogenous mitochondrial transplantation attenuates oxidative stress-driven retinal degeneration in a sodium iodate - induced mouse model.

Seok Jae Lee, Sung-Eun Noh, Jeong Hun Kim.

  Age-related macular degeneration (AMD) is a degenerative retinal disease initiated by dysfunction of the retinal pigment epithelium (RPE), in which age-related mitochondrial impairment, oxidative stress, chronic inflammation, and complement activation collectively drive outer retinal dysfunction and RPE atrophy, ultimately leading to progressive central vision loss. Accumulating evidence indicates that mitochondrial abnormalities, including excessive reactive oxygen species (ROS) production, mitochondrial fragmentation, and inflammatory signaling, play a central role in AMD pathogenesis. In this study, we investigated the therapeutic potential of exogenous mitochondrial transplantation using a sodium iodate (SI)-induced retinal degeneration model that recapitulates key pathological features of dry AMD. In ARPE-19 cells, SI-induced oxidative stress triggered mitochondrial fragmentation, inflammasome activation, and tight junction disruption, whereas delivery of mitochondria isolated from bone marrow-derived mesenchymal stem cells attenuated mitochondrial dysfunction and preserved RPE barrier integrity by suppressing oxidative and inflammatory signaling. Consistent with these in vitro findings, intravitreal mitochondrial transplantation in SI-treated mice attenuated RPE shedding/migration and outer nuclear layer disorganization while suppressing retinal oxidative stress, inflammatory cytokine expression, and complement activation. Importantly, mitochondrial transplantation mitigated the decline in retinal function, as assessed by electroretinography and optokinetic response testing, without fully restoring responses to control levels. Collectively, these results support exogenous mitochondrial transplantation as a promising cell-free therapeutic strategy to attenuate oxidative stress-driven retinal degeneration by modulating mitochondrial dysfunction and associated inflammatory pathways in AMD.

Keywords:  Age-related macular degeneration; Bone marrow–derived mesenchymal stem cells; Mitochondrial dysfunction; Outer retinal degeneration; Retinal aging; Retinal pigment epithelium

DOI:  https://doi.org/10.1016/j.neurobiolaging.2026.07.002
Transl Neurodegener. 2026 Jul 08. pii: 30. [Epub ahead of print]15(1):

Plant-derived mitochondria mitigate aging-related neurodegeneration by reprogramming microglial mitochondrial energy metabolism.

Yun Teng, Chao Luo, Qingbo Xu, Jingyao Mu, Lucy Teng, Hongjia Qian, Yinan Huang, Minmin Liu, Lifeng Zhang, Juw Won Park, Jae Yeon Hwang, Maiying Kong, Jun Yan, Michael L Merchant, Huang-Ge Zhang.

   BACKGROUND: Intercellular mitochondrial transfer is pivotal in both healthy and pathological states. Supplementing healthy mitochondria is emerging as a promising therapeutic approach for various diseases. Non-immunogenic edible plants, which contain mitochondria, offer a novel avenue for such therapies.
METHODS: Mitochondria were isolated from several commonly consumed edible plants (P-Mit) using differential centrifugation followed by sucrose gradient ultracentrifugation. The distribution of P-Mit, particularly in the brain, was examined with a mitochondrial membrane-potential dye and an imaging system. As a proof of concept, the molecular interactions underlying turmeric-derived mitochondria (T-Mit) uptake by microglia were elucidated through affinity precipitation coupled with mass spectrometry. By labeling with gold-nanoparticles in a distinct triangular or spherical shape followed by electron microscopy and energy dispersive spectroscopy analysis, we demonstrated the physical fusion of T-Mit and animal mitochondria in microglia. Mitochondrial functions such as superoxide levels, ATP-linked mitochondrial respiration, glycolysis and electron transport chain activity were assessed to determine the impact of T-Mit on aging-related microglial dysfunction. Next-generation small RNA sequencing revealed the underlying mechanism by which T-Mit-derived small RNAs modulate the expression of NADH dehydrogenase (ND) genes in microglia.
RESULTS: Orally administered T-Mit travelled from the gut to the brain in aged male mice, where they fused with microglial mitochondria (M-Mit), reprogramming M-Mit energy metabolism and reversing aging-related cognitive dysfunction. Specifically, T-Mit was taken up by microglia via the phagocytic receptor TREM2. Subsequently, T-Mit fused with M-Mit in a mitofusin 1-dependent manner. The T-Mit microRNAs Tae-miR319 and Osa-miR166a-3p then integrated into M-Mit, inhibiting the expression of complex I subunits ND4 and ND5. This inhibition alleviated reverse electron transport (RET) at complex I, reducing reactive oxygen species (ROS) production and facilitating ATP production, ultimately rescuing aging-related cognitive decline. Data from elderly human subjects also showed overactivation of the RET process and overproduction of ROS, accompanied by low ATP levels in microglia.
CONCLUSIONS: Our findings fundamentally alter our understanding of the regulation of mammalian mitochondrial biology by P-Mit and may lead to P-Mit-based transfer therapy for preventing or treating human mitochondrial disorder-related diseases.

Keywords:  Aging-related neurodegeneration; Cardiolipin; Cross-kingdom mitochondrial fusion; Microglia mitochondrial metabolism; Mitochondria transfer therapy; NADH dehydrogenase (Complex I); Plant mitochondrial microRNAs; Plant mitochondria; Reactive oxygen species (ROS); Reverse electron transport (RET)

DOI:  https://doi.org/10.1186/s40035-026-00565-1
Int J Biol Macromol. 2026 Jul 05. pii: S0141-8130(26)03309-X. [Epub ahead of print] 153369

A microfluidic platform for isolating functional mitochondria and restoring bioenergetic activity in hypoxia-injured cardiomyocytes.

Hsu Yen-Chin, Uyen Thi Nhat Nguyen, Thierry Burnouf, Han-Yun Hsieh, Yu-Jui Fan.

  Hypoxic stress is known to severely impair mitochondrial function in cardiomyocytes, leading to disruption of intracellular bioenergetic homeostasis, reduced ATP production, and compromised cellular performance. Because cardiomyocytes rely heavily on mitochondrial oxidative metabolism to meet their high energy demands, mitochondrial dysfunction represents a central mechanism underlying hypoxia-induced cardiac injury. In this study, a microfluidic-based platform was developed for mitochondrial isolation and to investigate whether the delivery of functionally preserved mitochondria could enhance mitochondrial bioenergetic function in hypoxia-injured cardiomyocytes. Human AC16 cardiomyocytes were used as the experimental model. Mitochondria were isolated using a centrifugal microfluidic disruption system operated under optimized centrifugation conditions and were directly compared with mitochondria obtained using a commercial isolation kit. Hypoxic injury was induced by culturing AC16 cells at 1% O₂ for 24 h. Mitochondrial incorporation and functional status were evaluated using MitoTracker staining, JC-1 analysis, intracellular ATP quantification, and Seahorse XF mitochondrial stress tests. Microfluidic devices can be used to extract mitochondria from healthy cells, and this method achieves similar functional results to mitochondria extracted using commercial reagents. Hypoxic cells show a significant decrease in cell membrane potential and overall respiratory capacity. Returning the extracted mitochondria to hypoxic cells shows partial recovery of mitochondrial function. Seahorse analysis reveals partial recovery of basal respiration, maximal respiration, reserve respiration, and ATP-coupled respiration, although not reaching the levels of healthy cells. This demonstrates the effectiveness of this method. These results indicate that mitochondria isolated using a microfluidic approach remain functionally competent and are capable of partially improving mitochondrial bioenergetic function in hypoxia-injured cardiomyocytes. The proposed microfluidic platform provides a controllable and reproducible strategy for mitochondrial isolation and functional evaluation and may serve as a useful tool for studying mitochondrial dysfunction and recovery under hypoxic conditions.

Keywords:  Cardiomyocytes; Hypoxia; Microfluidics; Mitochondrial bioenergetics; Mitochondrial delivery; Mitochondrial isolation

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.153369