Melatonin rescues cell respiration impaired by hypoxia/reoxygenation in aortic endothelial cells and affects the mitochondrial bioenergetics targeting the FF-ATPase.

Melatonin is evaluated as a potential molecular therapy to counteract mitochondrial dysfunction caused by hypoxia/reoxygenation (H/R) in aortic endothelial cells (pAECs). The mitochondrial permeability transition pore (mPTP) opening undergoes a desensitizing action coupled with a reduction of superoxide anion production in mitochondria treated with melatonin. The effect on mPTP has been attributed to the direct interaction of melatonin with the hydrophilic F domain of Ca-activated FF-ATPase. Mutual exclusion analysis highlights an overlapping binding site between melatonin and the specific F inhibitor NBD-Cl. The results are corroborated by melatonin inhibition of ATPase activity of the purified F domain in the presence of Ca, but not in the presence of natural cofactor Mg. Moreover, the impairment of bioenergetics parameters in pAECs metabolism and the increase of oxidative stress arising by H/R injury have been rescued in cells protected by melatonin treatment.