1. Mitochondria transplantation alleviates cardiomyocytes apoptosis through inhibiting AMPKα-mTOR mediated excessive autophagy.
- Author
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Jin N, Zhang M, Zhou L, Jin S, Cheng H, Li X, Shi Y, Xiang T, Zhang Z, Liu Z, Zhao H, and Xie J
- Subjects
- Animals, Humans, Male, Mice, Doxorubicin pharmacology, Heart Failure metabolism, Mice, Inbred C57BL, AMP-Activated Protein Kinases metabolism, Apoptosis, Autophagy, Mesenchymal Stem Cells metabolism, Mitochondria metabolism, Mitochondria transplantation, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, TOR Serine-Threonine Kinases metabolism
- Abstract
The disruption of mitochondria homeostasis can impair the contractile function of cardiomyocytes, leading to cardiac dysfunction and an increased risk of heart failure. This study introduces a pioneering therapeutic strategy employing mitochondria derived from human umbilical cord mesenchymal stem cells (hu-MSC) (MSC-Mito) for heart failure treatment. Initially, we isolated MSC-Mito, confirming their functionality. Subsequently, we monitored the process of single mitochondria transplantation into recipient cells and observed a time-dependent uptake of mitochondria in vivo. Evidence of human-specific mitochondrial DNA (mtDNA) in murine cardiomyocytes was observed after MSC-Mito transplantation. Employing a doxorubicin (DOX)-induced heart failure model, we demonstrated that MSC-Mito transplantation could safeguard cardiac function and avert cardiomyocyte apoptosis, indicating metabolic compatibility between hu-MSC-derived mitochondria and recipient mitochondria. Finally, through RNA sequencing and validation experiments, we discovered that MSC-Mito transplantation potentially exerted cardioprotection by reinstating ATP production and curtailing AMPKα-mTOR-mediated excessive autophagy., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
- Published
- 2024
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