Fig. 2: Mitophagy promotes oxidative stress in ischemic cardiomyopathy.
From: Mitophagy in ischemic heart disease: molecular mechanisms and clinical management
The inflammatory signals in myocardial cells usually begin with the accumulation of myocardial cell mitochondria caused by stress response. Research has shown that YQHX can alleviate hypoxia induced damage by targeting mitophagy. On the other hand, quercetin alleviates mitochondrial oxidative stress through DNA-PKcs-SIRT5. DUSP12 can inhibit cell apoptosis caused by hypoxia through HSPB8. Inhibition of Parkin mediated mitophagy leads to excessive accumulation of mitochondrial ROS, which in turn promotes the progression of progressive myocardial injury and heart failure. Under low oxygen conditions, mitophagy regulates myocardial ischemia-reperfusion injury through the HIF/BNIP3 pathway. Similarly, studies have shown that JMJD5 can alleviate myocardial cell damage by regulating the HIF-BNIP3 pathway. Other studies have shown that exosomes rich in Sirt6 inhibit cell pyroptosis in AIM2 and enhance mitophagy through the p62 and Beclin-1 pathways, thereby improving myocardial cell damage. The knockdown of ZIP7 has also been confirmed to reduce mitochondrial ROS generation and myocardial infarction by increasing Zn2+in mitochondria, leading to mitochondrial depolarization, as well as the accumulation of PINK1 and Parkin in mitochondria.
