It was a surprising discovery when mitochondria,
as the power houses of cells, were also found to synthesize the potent
mitochondrial targeted antioxidant, melatonin. The melatonin synthetic enzyme serotonin
N-acetyltransferase (SNAT) was found in matrix and also in the intermembrane space
of mitochondria. We hypothesize that the melatonin synthesis occurs in the matrix
due to substrate (N-acetyl co-enzyme A) availability while the intermembrane
space may serve as the recycling pool of SNAT to regulate the melatonin
circadian rhythm. Another surprise was that the melatonin membrane receptors,
including MT1 and MT2, were also present in mitochondria. The protective
effects of melatonin against neuronal injury induced by brain ischemia/reperfusion
were proven to be mainly mediated by mitochondrial melatonin receptors rather
than the cell surface membrane receptors which is contrary to the classical
principle. In addition, melatonin metabolic enzyme has also been identified in
the mitochondria. This enzyme can convert melatonin to N-acetylserotonin to
strengthen the antitumor effects of melatonin. Thus, mitochondria are the
generator, battle ground and metabolic sites of melatonin. The biological
significance of the strong association between mitochondria and melatonin
should be intensively investigated.
Liver-targeted liposomes for codelivery of curcumin and combretastatin A4 phosphate: preparation, characterization, and antitumor effects