bims-mitrat 2025-07-06 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2025–07–06
seven papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Biotechnological approaches and therapeutic potential of mitochondria transfer and transplantation.
Powering Up the Brain: Intercellular Mitochondrial Quality Control and Its Implication in Stroke.
Gelated microvesicle-mediated delivery of mesenchymal stem cell mitochondria for the treatment of myocardial infarction.
Mitochondrial transplantation: adaptive bio-enhancement.
Mechanisms of electroacupuncture-induced neuroprotection in acute stroke rats: the role of astrocyte-mediated mitochondrial transfer.
Mitotherapy attenuates sepsis-induced brain injury in rats subjected to cecal ligation and puncture: Role of SIRT-1/PGC-1α network.
Cardioprotective strategies against doxorubicin-induced cardiotoxicity: A review from standard therapies to emerging mitochondrial transplantation.

Nat Commun. 2025 Jul 01. 16(1): 5709

Biotechnological approaches and therapeutic potential of mitochondria transfer and transplantation.

Gokhan Burcin Kubat, Pasquale Picone, Erkan Tuncay, Leila Aryan, Antonella Girgenti, Laura Palumbo, Ibrahim Turkel, Firat Akat, Keshav K Singh, Domenico Nuzzo.

Mitochondrial dysfunction contributes to aging and diseases like neurodegeneration and cardiovascular disorders. Mitochondria transfer and transplantation (MTT) represent promising therapeutic strategies aimed at restoring cellular function by introducing functional mitochondria into damaged cells. However, challenges like transfer efficiency, stability, and cellular integration limit clinical application. Recent biotechnological advances-such as liposomes, extracellular vesicles, and surface modifications-enhance mitochondrial protection, targeting, and biocompatibility. This Perspective highlights recent progress in MTT, its therapeutic potential, and current limitations. We also discuss the need for scalable, clinically translatable approaches and appropriate regulatory frameworks to realize the full potential of mitochondria-based nanotherapies in modern medicine.

DOI: https://doi.org/10.1038/s41467-025-61239-6
Curr Neuropharmacol. 2025 Jun 30.

Powering Up the Brain: Intercellular Mitochondrial Quality Control and Its Implication in Stroke.

Xinyu Zhou, Shenzhe Wu, Tianxi Huang, Yue Li, Jianhong Yang, Zhen Gu, Xiangnan Zhang.

  Mitochondria are critical for neuronal survival and function, and their dysregulation is closely related to the incidence and prevalence of various neurological disorders, including stroke. Mitochondrial quality control (MQC) is vital for maintaining mitochondrial integrity, particularly in neurons. Under ischemic conditions, neurons evolve a range of adaptive strategies to preserve mitochondria function dynamically, either by generating functional mitochondria or by eliminating dysfunctional ones via autophagy, both of which play key roles in keeping neuronal survival under the conditions of stroke. Besides these intracellular strategies, the intercellular mechanisms underlying MQC have been observed in the nervous system. Functional mitochondria from healthy cells can be supplemented to ischemic neurons in distinct manners and thus restore the mitochondrial network of recipient cells. Conversely, injured neurons release dysfunctional mitochondria, which can be further degraded by adjacent glial cells. Alternatively, the discarded mitochondria act as a threat to surrounding cells and can disrupt the homeostasis of the nervous system. In this review, the key discoveries in intercellular MQC in the nervous system were summarized, and further discussed the implications of intercellular MQC strategies for stroke therapy.

Keywords:  Intercellular mitochondrial quality control; intercellular mitochondrial transport; stroke.; trans mitophagy

DOI:  https://doi.org/10.2174/011570159X388351250620065716
Proc Natl Acad Sci U S A. 2025 Jul 08. 122(27): e2424529122

Gelated microvesicle-mediated delivery of mesenchymal stem cell mitochondria for the treatment of myocardial infarction.

Qi Chu, Dong He, Wenqi Xie, Shichun Li, Zixuan Dong, Xiaoling Fu.

  Mitochondrial dysfunction is closely linked to cardiomyocyte injury following myocardial infarction (MI). While mitochondrial transplantation is a promising therapeutic strategy, challenges remain in maintaining mitochondrial structural integrity, enhancing delivery efficiency, and increasing the mitochondrial supply. Herein, we developed a gelated microvesicle-based mitochondria delivery system (Mito@Microgels) for transplanting mesenchymal stem cell mitochondria, addressing the aforementioned issues. Further decoration of phosphatidylserine on the surface of Mito@Microgels boosted cellular uptake efficiency by cardiomyocytes. These Mito@Microgels effectively deliver active mitochondria to cardiomyocytes, improving the mitochondrial network architecture and function and consequently reducing the cellular injury induced by oxidative stress. Moreover, Mito@Microgels attenuated the inflammatory phenotype of macrophages, helping resolve excessive local inflammation. In vivo animal studies using a rat MI model further validated the therapeutic efficacy of the Mito@Microgels, as evidenced by improved myocardial function, prevention of infarcted left ventricular wall thinning, and increased cardiomyocyte survival. Our study introduces an efficient mitochondrial delivery strategy with significant potential for cardiac repair post-MI and other mitochondria-related diseases.

Keywords:  gelated microvesicle; mitochondrial delivery; myocardial infarction; myocardiocyte rescue

DOI:  https://doi.org/10.1073/pnas.2424529122
Cell Death Dis. 2025 Jul 01. 16(1): 473

Mitochondrial transplantation: adaptive bio-enhancement.

Xiaomeng Lu.

Mitochondria, often referred to the powerhouse of the cell, are essential for cellular energy production, and their dysfunction can profoundly affect various organs. Transplantation of healthy mitochondria can restore the bioenergetics in diseased cells and address multiple conditions, but more potentials of this approach remain unclear. In this study, I demonstrated that the source of transplanted mitochondria is not limited by species, as exhibit no significant responses to mitochondria derived from different germlines. Moreover, I identified that metabolic compatibility between the recipient and exogenous mitochondria as a crucial factor in mitochondrial transplantation, which confers unique metabolic properties to recipient cells, enabling them to combat different diseases. Additionally, my findings indicated competitive interactions among mitochondria with varying functions, with more bioenergetic-active mitochondria yielded superior therapeutic benefits. Notably, no upper limit for the bioenhancement provided by exogenous mitochondria has been identified. Based on these insights, I proposes a novel therapeutic approach-adaptive bioenhancement through mitochondrial transplantation.

DOI: https://doi.org/10.1038/s41419-025-07643-8
Cell Commun Signal. 2025 Jul 01. 23(1): 316

Mechanisms of electroacupuncture-induced neuroprotection in acute stroke rats: the role of astrocyte-mediated mitochondrial transfer.

Yang Guo, Tiancong Fu, Yupei Cheng, Yuxuan Li, Runchen Zhang, Qingtao Ma, Guanran Wang, Wenhua Ning, Wen Fan, Juntao Yang, Mengxiong Zhao, Bohan Liu, Can Wang, Liang Gao, Zhifang Xu, Yi Guo, Xiaoyu Dai, Jiangwei Shi.

   BACKGROUND: Ischemic stroke significantly threatens human health, and current treatments remain limited, necessitating novel strategies. Mitochondrial transfer between neurons represents a crucial endogenous neuroprotective mechanism.
OBJECTIVE: This study investigated whether electroacupuncture enhances mitochondrial transfer from astrocytes to damaged neurons during acute cerebral ischemia, promoting neuroprotection.
METHODS: A middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro were employed. Neurobehavioral assessments, electron microscopy, multiplex immunofluorescence, tissue quantification, western blotting, qRT-PCR, transcriptomics, and proteomics were conducted to evaluate mitochondrial distribution, function, and intercellular transfer under electroacupuncture preconditioning and intervention.
RESULTS: Electroacupuncture significantly improved neurological outcomes and reduced brain tissue damage in MCAO rats. It facilitated mitochondrial transfer from astrocytes to neurons, increased functional mitochondria within neurons, and reduced neuronal apoptosis. These effects may involve regulation of the CD38-cADPR-Ca2 + signaling pathway and proteins associated with tunneling nanotubes (TNTs), such as F-actin, Miro1, TRAK1, and KIF5b.
CONCLUSION: Electroacupuncture enhances mitochondrial transfer and function, exerting neuroprotective effects during acute ischemic stroke. This study highlights the potential of electroacupuncture as a therapeutic approach and identifies novel targets for brain protection strategies.

Keywords:  Astrocyte; Electroacupuncture; Mitochondrial transfer; Stroke

DOI:  https://doi.org/10.1186/s12964-025-02287-9
Iran J Basic Med Sci. 2025 ;28(8): 1065-1074

Mitotherapy attenuates sepsis-induced brain injury in rats subjected to cecal ligation and puncture: Role of SIRT-1/PGC-1α network.

Behnaz Mokhtari, Alireza Alihemmati, Soleyman Bafadam, Solmaz Boraghi, Reza Badalzadeh, Ata Mahmoodpoor.

   Objectives: Sepsis-induced brain injury poses a critical challenge with limited therapeutic options. Mitochondrial dysfunction is a central contributor to this pathogenesis. The current work aimed to examine the effects of mitochondrial transplantation, termed "mitotherapy", on sepsis-induced brain injury using a cecal ligation and puncture (CLP) rat model.
Materials and Methods: Male Wistar rats (n=40, 12 weeks old, weighing 250-300 g) were allocated into groups with or without CLP-induced sepsis, receiving mitotherapy via single or two repetitive injections post-CLP. In recipient groups, mitochondria harvested from donor rats were injected intravenously (400 μl of mitochondrial suspension containing 7.5×106 mitochondria/ml of respiration buffer). Twenty-four hours post-operation, the behavioral phenotype was tested by using the Murine Sepsis Score (MSS). Brain morphological examination was conducted using Hematoxylin and Eosin staining. Mitochondrial function was measured by evaluating membrane potential, reactive oxygen species production, and adenosine triphosphate content. The expression of genes regulating mitochondrial biogenesis (SIRT-1, PGC-1α) and fission/fusion (Drp1, Mfn1, Mfn2) was determined via real-time polymerase chain reaction. The levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) were measured using Enzyme-Linked Immunosorbent Assay.
Results: Mitotherapy reduced MSS and alleviated histopathological changes associated with sepsis-induced brain injury. Furthermore, it restored mitochondrial functional indices, up-regulated genes involved in mitochondrial biogenesis and fusion, and reduced inflammatory cytokine levels (P<0.05). Repetitive injections provided greater therapeutic benefits than a single injection.
Conclusion: Mitotherapy mitigated sepsis-induced brain injury by improving mitochondrial function, biogenesis, and dynamics within the SIRT-1/PGC-1α network and concurrently suppressing inflammation. Repetitive injections exhibited enhanced potency, suggesting a novel avenue for managing sepsis-associated brain dysfunction.

Keywords:  Brain; Mitochondria; Mitotherapy; Neuroprotection; Sepsis

DOI:  https://doi.org/10.22038/ijbms.2025.84848.18363
Biomed Pharmacother. 2025 Jul 03. pii: S0753-3322(25)00509-8. [Epub ahead of print]189 118315

Cardioprotective strategies against doxorubicin-induced cardiotoxicity: A review from standard therapies to emerging mitochondrial transplantation.

Kanako Ito-Hagiwara, Jun Hagiwara, Yusuke Endo, Lance B Becker, Kei Hayashida.

  Doxorubicin (DOX), a widely used chemotherapeutic agent, is effective against a broad spectrum of malignancies but is limited by its dose-dependent and potentially irreversible cardiotoxicity. DOX-induced cardiomyopathy can lead to progressive cardiac dysfunction and heart failure, significantly impacting patient survival and quality of life. The pathogenesis of this cardiotoxicity is multifactorial, involving excessive reactive oxygen species production, mitochondrial dysfunction, calcium dysregulation, ferroptosis, DNA damage, impaired autophagy, inflammation, and cardiomyocyte death. Current cardioprotective strategies-including β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and dexrazoxane-provide only partial protection and are insufficient to fully prevent long-term cardiac damage. In recent years, mitochondria-targeted therapies have gained attention due to the central role of mitochondrial injury in DOX cardiotoxicity. Therapeutic interventions aimed at modulating mitophagy, mitochondrial dynamics, oxidative stress, and inflammation have shown promise in preclinical studies. Among these, mitochondrial transplantation (MTx) represents an innovative and emerging strategy that directly restores mitochondrial function in injured cardiomyocytes. Preclinical studies demonstrate that MTx improves cardiac function, attenuates oxidative stress, reduces apoptosis, and enhances metabolic recovery in models of this cardiotoxicity. However, several critical challenges remain, including the long-term fate of transplanted mitochondria, immune compatibility, delivery methods, and safety. This narrative review provides a comprehensive overview of the molecular mechanisms underlying anthracycline-induced cardiac injury, evaluates current and emerging therapeutic approaches, and highlights the potential of MTx as a novel, mechanistically targeted therapy. Further research is needed to overcome translational barriers and evaluate clinical efficacy in human studies.

Keywords:  Cardioprotection; Cardiotoxicity; Doxorubicin; Mitochondria targeted therapy; Mitochondria transplantation

DOI:  https://doi.org/10.1016/j.biopha.2025.118315