Fig. 3: Mitophagy promotes myocardial cell death.
From: Mitophagy in ischemic heart disease: molecular mechanisms and clinical management
The research results indicate that TBC1D15 plays a key role in myocardial injury through mitophagy regulated by Fis1/RAB7. Parkin inhibits mPTP opening and myocardial cell necrosis by catalyzing the ubiquitination of CypD. Upregulation of MCU helps to inhibit calpain/OPA-1 mediated mitophagy and suppress excessive cell apoptosis through OPA1. Thyroid hormones can provide cardiac protection by enhancing PINK1 dependent mitophagy. MiR-494-3p can target and negatively regulate PGC1- α mediated mitophagy in cardiomyocytes, inhibiting cardiomyocyte apoptosis. Rich hydrogen saline alleviates inflammation and cell apoptosis in myocardial I/R injury through PINK1/Parkin mediated mitophagy. RR can inhibit cell apoptosis by inhibiting USP33 to promote mitophagy. Similarly, PPENK can promote mitophagy and reduce myocardial ischemia-reperfusion injury through the PINK1 Parkin pathway. Drp1 induced mitophagy disruption has tolerance to hypoxia induced damage. RIPK3 inhibits AMPK to prevent PINK1-PRKN induced mitophagy, thereby promoting myocardial cell necrosis. Ischemia reperfusion can trigger upregulation of RIPK3, promote phosphorylation of FUNDC1, and induce cell apoptosis.
