Mitochondrial dynamics in myocardial ischemia/reperfusion injury: Effects of melatonin

Timely reperfusion during myocardial infarction paradoxically leads to ischemia/reperfusion (I/R) injury. Mitochondrial quality control has emerged as a key participant in regulation of this process. The aims of this review are to briefly summarize current evidence for the role of mitochondrial quality control in I/R injury and to evaluate whether the cardioprotective actions of melatonin, a potent free radical scavenger and antioxidant, can be attributed to its effects on these processes. Using a variety of experimental models, in vivo and in vitro, melatonin-induced cardioprotection has been demonstrated to be associated with attenuation or reversal of the harmful effects of I/R on parameters of mitochondrial quality control as evidenced by (i) upregulation of mitochondrial fusion and inhibition of fission, particularly Drp1 expression and translocation from the cytosol to the mitochondria; (ii) changes in both the conventional and alternative mitophagy pathways. Melatonin significantly upregulates mitochondrial biogenesis and the expression of sirtuins 1, 3 and 6 and has a beneficial effect on mitochondrial-endoplasmic reticulum interaction in I/R. A novel observation is the ability of melatonin to stimulate intercellular transfer of mitochondria between damaged cells, although this has not yet been demonstrated in myocardial I/R. Melatonin treatment has profound effects on the diabetic heart: it reverses the significant reduction in function and inhibits the progression of diabetic cardiomyopathy which was associated with a significant effect on mitochondrial quality control, as evidenced by a reduction in fission. In summary, available evidence supports a major role for mitochondrial quality control in the beneficial actions of melatonin in the I/R heart.