Figure 2.

Three mechanisms of mitophagy and the ways they intervene in treating CVDs. Three mechanisms of mitophagy include mitochondrial outer membrane receptor-mediated (such as Bnip3, Nix and Fundc1), Pink1/Parkin pathway, and lipid receptor-mediated mechanisms (such as MtCK, NDPK-D). The LC3 is located in the phagophore and binds to the corresponding receptor. The LC3 can bind to substances of different mitophagy mechanisms. To demonstrate the mitophagy occurring in CVDs, cardiomyocytes (CM) and Pink1/Parkin pathway were used to intervene in heart failure (HF) and myocardial hypertrophy (MH) by inhibitors. In Pink1/Parkin-dependent mitophagy, the Pink 1 accumulated on the damaged mitochondria is activated and recruits Parkin for phosphorylation. The phosphorylated Parkin binds to the ubiquitin attached to outer OMM, and finally binds to LC3 for mitophagy. The Bnip3 and Nix can directly bind LC3 and promote mitophagy. MtCK and NDPK-D as specific transporters can also directly bind LC3 for mitophagy to eliminate damaged mitochondria. The inhibitor acts on Pink1/Parkin pathway, and then prevents excessive mitophagy and improves mitochondrial function, thereby maintaining the healthy levels of cells associated with CVDs. OMM, outer mitochondrial membrane; IMS, inter membrane space; IMM, inner mitochondrial membrane.