Exercise-induced intercellular mitochondrial transfer: Redox signaling as a candidate regulatory mechanism.

Intercellular mitochondrial transfer has been recognized as an important mechanism for maintaining tissue homeostasis and adapting to stress. Mitochondria can cross cellular boundaries through tunneling nanotubes, extracellular vesicles, and free mitochondrial release. However, the physiological signals coordinating these pathways remain poorly defined. Exercise is a potent inducer of transient redox signaling, generating superoxide and hydrogen peroxide while modulating mitochondrial dynamic remodeling. This review integrates exercise redox biology with redox regulation of transfer machinery characterized in non-exercise models, proposing that exercise-induced redox signaling may function as a candidate regulatory mechanism. The framework emphasizes bidirectional redox coordination, in which oxidant pulses may activate export in donor cells and prepare recipient cells for uptake and antioxidant defense. Exercise-induced mitochondrial transfer has been directly demonstrated in the brain, while observations in skeletal muscle, adipose tissue, and heart remain suggestive but have not been confirmed in exercise models. These findings support a framework in which intercellular mitochondrial transfer contributes to metabolic signaling, antioxidant defense, and distributed quality control across organs. This model represents a working hypothesis requiring direct experimental validation through lineage tracing, tissue-specific mitochondrial reporters, and intravital imaging.