ABSTRACT
In the last decade, numerous publications have documented the protective actions ofmelatonin against a vast array of conditions in which free radical damage is a component(e.g., ischemia/reperfusion injury, aging and age-associated diseases, toxin exposure, lipopolysaccharide exposure). Melatonin is a highly ubiquitous direct free radical scavenger and indirect antioxidant. Mitochondria appear to constitute the greatest source of oxidants. Oxidatively damaged mitochondria are unable to maintain the energy demands of the cell, which leads to further production of free radicals. Cellular energy deficits caused by declines in mitochondrial function can impair normal cellular activities and compromise the cell’s ability to adapt to various physiologic stresses. This review summarizes the role of melatonin in mitochondrial physiology and describes the beneficial actions of melatonin against mitochondrial dysfunction in conditions such as ischemia/reperfusion injury and aging, in which oxygen free radicals have a major role. In addition, recent observations documenting the ability of melatonin to stimulate electron transport and ATP production in the inner mitochondrial membrane also have relevance for melatonin as an agent that could alter the processes of aging. Finally, this report describes data showing that melatonin is not only a pharmacologically useful free radical scavenger but that it also functions in this capacity at physiologic concentrations. The discovery of new actions of melatonin in mitochondria supports a novel mechanism that explains the protective effects of melatonin on cells.
