Role of melatonin in the regulation of autophagy and mitophagy: a review.

Oxidative stress plays an essential role in triggering many cellular processes including programmed cell death. Proving a relationship between apoptosis and reactive oxygen species has been the goal of numerous studies. Accumulating data point to an essential role for oxidative stress in the activation of autophagy. The term autophagy encompasses several processes including not only survival or death mechanisms, but also pexophagy, mitophagy, ER-phagy or ribophagy, depending of which organelles are targeted for specific autophagic degradation. However, whether the outcome of autophagy is survival or death and whether the initiating conditions are starvation, pathogens or death receptors, reactive oxygen species are invariably involved. The role of antioxidants in the regulation of these processes, however, has been sparingly investigated. Among the known antioxidants, melatonin has high efficacy and, in both experimental and clinical situations, its protective actions against oxidative stress are well documented. Beneficial effects against mitochondrial dysfunction have also been described for melatonin; thus, this indoleamine seems to be linked to mitophagy. The present review 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.