Aim: 

To study the role of melatonin in mitochondrial function including mitochondrial oxygen flux, electron leak and reactive oxygen species production.

Methods: 

Using high-resolution respirometry, fluorometry and spectrophotometry we studied the effects of melatonin upon mitochondrial function. Mitochondria were prepared from mouse-liver cells and incubated in vitro with melatonin (1 nM to 1 mM).

Results: 

Melatonin decreased oxygen consumption, inhibited any increase in oxygen flux in the presence of ADP, reduced the membrane potential, and inhibited the production of superoxide anion and hydrogen peroxide. Melatonin also maintained the efficiency of oxidative phosphorylation and ATP synthesis whilst increasing the activity of the respiratory complexes (mainly complexes I, III, and IV). The effects of melatonin appeared to be due to its presence within the mitochondria, since kinetic experiments clearly showed its incorporation into these organelles.

Conclusions: 

Our results support that melatonin accomplishes mitochondrial homeostatic roles quite efficiently since it is able to reduce oxygen consumption and, thus reactive oxygen species production, whilst maintaining oxidative phosphorylation activity and ATP production. Due to the presence of melatonin in the mitochondria, the uncoupling-like effect of the indoleamine here reported may constitute a major mechanism to protect the mitochondria from oxidative damage.

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