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Extracellular mitochondria: a potential player involved in exercise health benefits

Year: 2025

Type: article

Abstract: Exercise is widely recognized as an effective nonpharmacological therapy for noncommunicable diseases, with its health benefits mediated in part by exerkines. Recently, extracellular mitochondria (ex-Mito) have been suggested as a player in mediating intercellular communication. While it is known that the health benefits of exercise involve the remodeling of mitochondria in multiple organs, the impact of exercise on circulating ex-Mito is poorly understood. Most existing studies have focused on cell-free circulating mitochondrial DNA, skeletal muscle-derived extracellular vesicles, or platelet-derived mitochondria, without focusing on other types of ex-Mito. The cellular origin of exercise-induced circulating ex-Mito and the role of each form (vesicle-enclosed, free, or as mitochondrial components) in mediating exercise's therapeutic effects are yet to be elucidated. This review aims to delve into the role of ex-Mito as potential players in exercise-related health benefits, paving the way for future research aimed at uncovering the molecular culprits of this nonpharmacological therapy, including mitochondrial transfer and transplantation. • Extracellular mitochondria mediate exercise-induced intercellular communication. • Extracellular mitochondria profile may vary with exercise type and metabolic status. • Extracellular mitochondria can be found freely, enclosed in vesicles or platelets, and as fragments. • Cfc-mtDNA content is responsive to exercise though its health impact is controversial. • Extracellular mitochondria emerge as therapeutic target for mitochondrial transplantation or transfer.

Source: Biochimie

DOI: 10.1016/j.biochi.2025.12.011

Authors: Mafalda Barbosa Pedrosa, Lúcio Lara Santos, Rita Ferreira, José Magalhães