Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

Figure 4

Regulatory mechanism of PINK/Parkin-mediated receptor-independent mitophagy during cell injury. Under the stimulation of inflammation/high glucose/high-fat conditions, excessive ROS will be generated. The permeability transition pore of the mitochondrial membrane will be excessively porous, the MMP will be severely reduced, and mitochondrial autophagy will disperse. Enzyme formation: In this abnormal state or in mitochondrial damage, activated PINK will recruit Parkin to the damaged mitochondria. Parkin will further mediate the ubiquitination of mitochondrial outer membrane proteins and promote the recognition of ubiquitinated mitochondria by adaptor proteins. Adaptor proteins link ubiquitin on the mitochondria to LC3 and LIR on the mitochondrial phagosomes, which eventually phagocytose and degrade the mitochondria.