bims-mitrat 2025-08-24 papers

Issue of 2025–08–24
five papers selected by

Adv Sci (Weinh). 2025 Aug 19. e06337

Mitochondrial Transplantation Augments the Reparative Capacity of Macrophages Following Myocardial Injury.

Yuning Zhang, Xiaolei Sun, Yawei Jin, Kanghui Chen, Lu Zhang, Xiong Gao, Mohan Li, Ze Yuan, Jianguo Jia, Aijun Sun, Junbo Ge.

The pathologically remodeled myocardial ischemic microenvironment, characterized by sustained hypoxia, metabolic insufficiency, and accumulation of inflammatory mediators, severely disrupts mitochondrial homeostasis. This dysfunction establishes a self-perpetuating cycle that impairs the coordinated healing cascade and compromises cardiac tissue repair following myocardial infarction (MI). To counteract these effects, a novel strategy of mitochondrial augmentation is proposed, whereby healthy exogenous mitochondria are introduced into macrophages to generate mitochondria-transplanted macrophages (Mito-T-Macros or MTMs), which can resist post-MI stress. Mitochondrial transplantation (MT) effectively induces macrophage polarization toward a reparative M2-like phenotype, thereby enhancing pro-healing functions, including migration, invasion, and phagocytosis. In vivo, MTM therapy enhances cardiac function after MI and attenuates left ventricular remodeling by reducing fibrosis, limiting apoptosis, and promoting angiogenesis. Mechanistically, MT accelerates the phenotypic transition of macrophages to a reparative state and prolongs their activity during the healing phase. Notably, a portion of the transplanted mitochondria are released from MTMs and subsequently internalized by cardiomyocytes, suggesting an additional mechanism of myocardial support. Overall, MT enhances the reparative capabilities of macrophages and contributes to the therapeutic efficacy of MTMs in ameliorating post-MI cardiac remodeling. These findings support MTM therapy as a promising and innovative approach for repairing myocardial injury following MI.

Keywords: macrophage reparative capacity; mitochondrial transplantation; myocardial infarction

DOI: https://doi.org/10.1002/advs.202506337

Reprod Med Biol. 2025 Jan-Dec;24(1):24(1): e12672

Significance of Mitochondrial Dynamics in Reproductive Physiology: Current and Emerging Horizons in Mitochondrial Therapy for Assisted Reproductive Technologies.

Sanath Udayanga Kankanam Gamage, Yoshiharu Morimoto.

Background: Mitochondria play a critical role in cellular bioenergetics and signaling, with particular importance in the context of reproductive biology. This review summarizes their role in reproduction and explores current and emerging mitochondrial therapies for fertility treatment.
Methods: A comprehensive literature search using terms like mitochondria, infertility, reproduction, gametes, mitochondrial replacement, and mitochondrial transplantation identified relevant studies on mitochondria's role in gametogenesis, fertilization, and early embryonic development in relevant databases. Selected publications were reviewed and summarized to present current and future mitochondrial therapies for fertility.
Main Findings: Mitochondrial dynamics and functions are critical for meeting the energy requirements of essential reproductive processes, including gametogenesis, fertilization, and early embryonic development. Dysregulation of mitochondrial function has been associated with a range of reproductive disorders, such as infertility, recurrent pregnancy loss, and maternally inherited mitochondrial diseases. Emerging therapeutic strategies, such as mitochondrial replacement therapy, antioxidant supplementation, and mitochondrial transplantation, offer promising avenues for overcoming these challenges and improving reproductive outcomes.
Conclusions: Utilizing mitochondrial-based therapies represents a promising and innovative approach in the advancement of fertility treatments. Ongoing research and clinical development in this area hold significant potential to enhance reproductive outcomes and improve the quality of life for individuals and couples facing fertility challenges.

Keywords: ascent; infertility; mitochondria; mitochondrial dysfunction; mitochondrial therapies for infertility; mitochondrial transplantation; reproductive aging

DOI: https://doi.org/10.1002/rmb2.12672

Mitochondrion. 2025 Aug 15. pii: S1567-7249(25)00074-1. [Epub ahead of print] 102077

Mitotherapy Restores mitochondrial function and improves cognitive deficits in Alzheimer's disease.

Tulika Gupta, Asha Rao, Veena Devi, Lalita Kumari, Akshita Negi, Munish Kumar, Ranjana Bharti, Bikash Medhi.

Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), contributing to cognitive decline. This study explores the therapeutic potential of mitochondrial transplantation in mitigating cognitive decline in AD. Structurally and functionally characterized mitochondria from young rat brains were intravenously transplanted into AD rats. Confocal imaging confirmed integration of exogenous tagged mitochondria into hippocampal tissue. Post-mitotherapy, we noted significant cognitive improvement by neurobehavioral tests and significant reduction in protein levels of amyloid precursor protein. Further mitochondrial functional parameters improved; reduced oxidative stress, improved mitochondrial membrane potential, and calcium homeostasis. These findings highlight mitotherapy as a promising strategy for treating Alzheimer's disease.

Keywords: AD Rat model; Alzheimer’s disease (AD); Cognitive improvement; Mitochondrial dysfunction; Mitotherapy

DOI: https://doi.org/10.1016/j.mito.2025.102077

Exp Dermatol. 2025 Aug;34(8): e70152

Platelet-Derived Extracellular Vesicles Alleviate Psoriatic Inflammation via Mitochondrial Transfer to Macrophages.

Bing Wang, Dandan Li, Chaolan Pan, Yumeng Wang, Yidong Tan, Yijun Yang, Haifei Liu, Zhirong Yao, Hui Zhang, Zhicheng Wang.

Platelet-rich plasma (PRP) is a safe, autologous plasma component abundant in cytokines and extracellular vesicles, frequently applied to treat inflammatory disorders. Although PRP demonstrates potential for psoriasis therapy, its underlying mechanism remains insufficiently understood. In this study, various PRP constituents were evaluated in an imiquimod (IMQ)-induced mouse model of psoriasis. PRP, platelet-derived extracellular vesicles (PEVs), and platelet-poor plasma (PPP) were isolated from mice and administered subcutaneously. The data showed that PEVs, rather than PPP, served as the principal anti-psoriatic factor. Furthermore, RNA sequencing and flow cytometry revealed that PEVs markedly suppressed M1 polarisation of macrophages, thereby mitigating psoriatic-like inflammation. In vitro, PEVs delivered encapsulated mitochondria to RAW264.7 cells in a concentration-dependent manner. These functional organelles enhanced oxidative phosphorylation and suppressed glycolysis, driving a metabolic shift favouring an anti-inflammatory phenotype and attenuating the inflammatory response. In conclusion, PEVs emerge as the primary PRP component responsible for inflammatory suppression in psoriasis. Notably, mitochondria transfer mediated by PEVs underscores a promising therapeutic avenue and provides novel insight into the role of platelet derivatives in inflammatory diseases.

Keywords: macrophage; mitochondria; platelet‐derived extracellular vesicles; platelet‐rich plasma; psoriasis

DOI: https://doi.org/10.1111/exd.70152