Transfer and fates of damaged mitochondria: role in health and disease

Intercellular communication is pivotal in mediating the transfer of mitochondria from donor to recipient cells. This process orchestrates various biological functions, including tissue repair, cell proliferation, differentiation and cancer invasion. Typically, dysfunctional and depolarized mitochondria are eliminated through intracellular or extracellular pathways. Nevertheless, increasing evidence suggests that intercellular transfer of damaged mitochondria is associated with the pathogenesis of diverse diseases. This review investigates the prevalent triggers of mitochondrial damage and the underlying mechanisms of mitochondrial transfer, and elucidates the role of directional mitochondrial transfer in both physiological and pathological contexts. Additionally, we propose potential previously unknown mechanisms mediating mitochondrial transfer and explore their prospective roles in disease prevention and therapy. Damaged mitochondria that escape degradation by mitophagy can be transferred to recipient cells, where they can either reinitiate mitophagic signaling, or fuse with the mitochondria of the target cell for reuse and utilization. Additionally, these damaged mitochondria release mitochondrial DNA (mtDNA) and mitochondrial reactive oxygen species (mtROS), which act as signal transducers. Here, we discuss common triggers of mitochondrial damage, and examine the mechanisms underlying mitochondrial transfer. We additionally investigate mitochondrial transfer in the context of disease and explore its role in disease prevention and treatment. image