Mitochondrial-derived vesicles: Gatekeepers of mitochondrial response to oxidative stress

Mitochondrial quality control (MQC) mechanisms are a series of adaptive responses that ensure the relative stability of mitochondrial morphology, quantity, and quality to preserve cellular survival and function. While MQC mechanisms range from mitochondrial biogenesis and fusion/fission to mitophagy, mitochondrial-derived vesicles (MDVs) may represent an essential component of MQC. MDVs precede mitochondrial autophagy and serve as the first line of defense against oxidative stress by selectively transferring damaged mitochondrial substances to the lysosome for degradation. In fact, the function of MDVs is dependent on the cargo, the shuttle route, and the ultimate destination. Abnormal MDVs disrupt metabolite clearance and the immune response, predisposing to pathological conditions, including neurodegeneration, cardiovascular diseases, and cancers. Therefore, MDV regulation may be a potential therapeutic for the therapy of these diseases. In this review, we highlight recent advances in the study of MDVs and their misregulation in various diseases from the perspectives of formation, cargo selection, regulation, and transportation.