Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease.

Melatonin, an endogenously synthesized indolamine, is a powerful antioxidant exerting beneficial action in many pathological conditions. Melatonin protects from oxidative stress in ischemic/reperfusion injury, neurodegenerative diseases, and aging, decreases inflammation, modulates the immune system, inhibits proliferation, counteracts the Warburg effect, and promotes apoptosis in various cancer models. Melatonin stimulates antioxidant enzymes in the cells, protects mitochondrial membrane phospholipids, especially cardiolipin, from oxidation thus preserving integrity of the membranes, affects mitochondrial membrane potential, stimulates activity of respiratory chain enzymes, and decreases the opening of mitochondrial permeability transition pore and cytochrome c release. This review will focus on the molecular mechanisms of melatonin effects in the cells during normal and pathological conditions and possible melatonin clinical applications.