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It is currently hypothesized that the ability of mitochondria to synthesize melatonin has been conserved throughout evolution such that the cells of every eukaryote produce melatonin in their mitochondria (138, 139), Melatonin synthesis in mitochondria puts it in a strategic location to neutralize the abundance of free radicals that are generated by this organelle, both due to leakage of electrons from the ETC as well as those produced because of enzymatic activities of oxidases, e.g., cytochrome c oxidase located in the inner mitochondrial membrane (Figure 4) (140)