Role of the Antioxidant Melatonin in Regulating Autophagy and Mitophagy

Autophagy is an evolutionarily conserved and highly regulated lysosomal related process that degrades oxidatively damaged, aberrant macromolecules and organelles for the purpose of maintaining homeostasis during stress. Several types of autophagy, including pexophagy, ER-phagy, or ribophagy, have been described, based on which organelles are targeted for specific autophagic degradation. Among them, mitophagy plays a crucial role in the well-being of cells, since it is the major degradative pathway in mitochondrial turnover. Although autophagy is emerging as an important mediator of pathological responses and engages in cross-talk with ROS (reactive oxygen species) and RNS (reactive nitrogen species) in both cell signaling and protein damage, the role of antioxidants in the regulation of these processes has been sparingly investigated. Melatonin, which is a ubiquitously acting antioxidant with protective actions against oxidative stress, also exhibits beneficial effects against mitochondrial dysfunction, suggesting a relation to mitophagy. This chapter focuses on data and the most recent advances related to the role of melatonin in health and disease, on autophagy activation in general, and on mitophagy in particular.