Fig. 1.

Overall path of cardiomyocyte death in ischemic heart disease and reperfusion. The ischemic heart environment and reperfusion induce myocardial cell death. Of these cell deaths, both apoptosis and necrosis are mediated by death receptors and mitochondria. These are divided into death receptor-mediated apoptosis and necroptosis, and mitochondria-mediated apoptosis and mitochondria-mediated necrosis, respectively. Both types of apoptosis involve the activation of Caspase-3/7, while the necroptosis is caused by permealization of the plasma membrane due to the activation of MLKL. Mitochondria-mediated necrosis is linked to the opening of mPTPs. In addition, an accumulation of damage to mitochondria occurs in ischemic heart disease, and it causes autophagy. The process proceeds as Parkin accumulates and PINK1 is transferred to the inside of the mitochondria