Aim: 

There is increasing evidence that mitochondria are intracellular targets for melatonin, which consistently improves mitochondrial function and ATP production. To further analyze the mechanism(s) involved in these actions of melatonin, measurement of mitochondrial bioenergetics, redox status, and ATP production were done.

Methods: 

Experiments in vitro were done with normal mitochondria obtained from rat and mouse liver and brain, incubated with melatonin. Experimental models of disease involving mitochondrial dysfunction, such as sepsis, Parkinson's disease, and aging, were also used. Among others, mitochondrial respiration, respiratory chain (ETC) activity, ATP production, free radical production, redox status, mitochondrial nitric oxide synthase activity, nitric oxide, and membrane potential, were measured.

Results: 

Melatonin enhances the ETC activity and ATP production in normal mitochondria in vitro and in vivo. Melatonin also decreases mitochondrial oxygen consumption and membrane potential, reduces superoxide anion and hydrogen peroxide formation, and maintains the ADP:O ratio. Melatonin in vivo also increases the ATP production, counteracting the mitochondrial dysfunction in sepsis, Parkinson's disease and aging.

Conclusions: 

Melatonin improves mitochondrial function and prevents their failure reducing the production of reactive oxygen species. The mechanism of action involves a reduction in the mitochondrial membrane potential and thus, in the electron leak, whereas increases the efficiency of the oxidative phosphorylation to maintain or even increase ATP production.

Supported by grants: RD06/0013/0008, P07-CTS-03135