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Melatonin protects the electron transport chain (ETC) by binding to the Fe-S cluster of NADPH dehydrogenase, reducing the generation of superoxide anion radicals (O2) caused by electron leakage, blocking the opening of the mitochondrial permeability transition pore (mPTP), and preventing apoptosis caused by cytochrome C leakage (Hardeland, 2017

As AIF deficiency potently compromises OXPHOS [32, 34], it is reasonable to speculate that AIF might be another target by which HIF downregulates mitochondrial respiration

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