Melatonin-mitochondria interplay in health and disease.

Abstract

The endosymbiotic hypothesis of mitochondrial origin posits that a metabolic partnership between an anaerobic hydrogen-dependent host and a respiring eubacterium gave rise to the proto-eukaryotic cell. This evolutionary event conferred aerobic energy metabolism but simultaneously introduced reactive oxygen species (ROS) and reactive nitrogen species (RNS), including peroxynitrite, as metabolic byproducts. Mitochondria maintain their own conserved genome, participate in ATP synthesis, thermogenesis, and programmed cell death, and have been implicated in neurodegenerative and neuromuscular disorders involving both nuclear and mitochondrial DNA alterations. Melatonin, recognized for its antioxidant and anti-inflammatory properties, has shown beneficial effects against oxidative and nitrosative stress in experimental and clinical settings, particularly in contexts of mitochondrial dysfunction. This review consolidates current knowledge on the mechanistic interactions between melatonin and mitochondrial pathology.

Mechanism

Melatonin exerts antioxidant and anti-inflammatory effects that suppress ROS and RNS generation, including peroxynitrite, thereby reducing oxidative and nitrosative stress associated with mitochondrial dysfunction.