Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing

Mitophagy serves as a cardinal regulator in the maintenance of mitochondrial integrity, function, and cardiovascular homeostasis, through the fine control and governance of cellular metabolism, ATP production, redox balance, and mitochondrial quality and quantity control. As a unique form of selective autophagy, mitophagy specifically recognizes and engulfs long-lived or damaged (depolarized) mitochondria through formation of the double-membraned intracellular organelles - mitophagosomes, ultimately resulting in lysosomal degradation. Levels of mitophagy are reported to be altered in pathological settings including cardiovascular diseases and biological ageing although the precise nature of mitophagy change in ageing and ageing-associated cardiovascular deterioration remains poorly defined. Ample clinical and experimental evidence has depicted a convincing tie between cardiovascular ageing and altered mitophagy. In particular, ageing perturbs multiple enigmatic various signal machineries governing mitophagy, mitochondrial quality, and mitochondrial function, contributing to ageing-elicited anomalies in the cardiovascular system. This review will update novel regulatory mechanisms of mitophagy especially in the perspective of advanced ageing, and discuss how mitophagy dysregulation may be linked to cardiovascular abnormalities in ageing. We hope to pave the way for development of new therapeutic strategies against the growing health and socieconomical issue of cardiovascular ageing through targeting mitophagy.