Intercellular Mitochondrial Transfer and Mitochondrial Transplantation in Cardiovascular Disease.

Mitochondria have traditionally been regarded as intracellular powerhouses; however, they are now recognized as dynamic intercellular signalling organelles capable of moving between cells to coordinate tissue adaptation and repair. In this Review we examine the emergence of mitochondria transfer as a fundamental mechanism of cardiovascular communication, with 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 that governs mitochondrial trafficking, such as mitochondrial Rho GTPase proteins, and cytoskeletal motor complexes. By reshaping cellular bioenergetics, redox homeostasis, metabolic signalling, and innate immune responses, transferred mitochondria exert profound effects on cardiovascular homeostasis and disease, by influencing ischemia-reperfusion injury, heart failure, vascular remodelling, 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, we outline a roadmap for translating mitochondria-based therapeutic strategies into precision cardiovascular medicine.