Although two main hypotheses of mitochondrial origin have been proposed, i.e., the autogenous and the endosymbiotic, only the second is being seriously considered currently. The '
hydrogen hypothesis' invokes metabolic symbiosis as the driving force for a symbiotic association between an anaerobic, strictly
hydrogen-dependent (the host) and an eubacterium (the symbiont) that was able to respire, but which generated molecular
hydrogen as an end product of anaerobic metabolism. The resulting proto-eukaryotic cell would have acquired the essentials of eukaryotic energy metabolism, evolving not only aerobic respiration, but also the physiological cost of the oxygen consumption, i.e., generation of
reactive oxygen species (ROS) and the associated oxidative damage. This is not the only price to pay for respiring
oxygen: mitochondria possess
nitric oxide (NO·) for regulatory purposes but, in some instances it may react with
superoxide anion radical to produce the toxic
reactive nitrogen species (RNS), i.e.
peroxynitrite anion, and the subsequent nitrosative damage. New mitochondria contain their own genome with a modified genetic code that is highly conserved among mammals. The transcription of certain mitochondrial genes may depend on the redox potential of the mitochondrial membrane. Mitochondria are related to the life and death of cells. They are involved in energy production and conservation, having an uncoupling mechanism to produce heat instead of
ATP, but they are also involved in programmed cell death. Increasing evidence suggest the participation of mitochondria in neurodegenerative and
neuromuscular diseases involving alterations in both nuclear (nDNA) and mitochondrial (
mtDNA)
DNA.
Melatonin is a known powerful
antioxidant and anti-inflammatory and increasing experimental and clinical evidence shows its beneficial effects against oxidative/nitrosative stress status, including that involving
mitochondrial dysfunction. This review summarizes the data and mechanisms of action of
melatonin in relation to mitochondrial pathologies.