Melatonin rescues cell respiration impaired by hypoxia/reoxygenation in aortic endothelial cells and affects the mitochondrial bioenergetics targeting the F1FO-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 F1 domain of Ca2+-activated F1FO-ATPase. Mutual exclusion analysis highlights an overlapping binding site between melatonin and the specific F1 inhibitor NBD-Cl. The results are corroborated by melatonin inhibition of ATPase activity of the purified F1 domain in the presence of Ca2+, but not in the presence of natural cofactor Mg2+. 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.

• Publication year

  2025

• Venue

  Redox Biology

• Publication date

  2025-03-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.redox.2025.103605PMID 40132239PMCID 11985001
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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