FIGURE 1.
The Occurrence and Mechanisms of Mitophagy. (A) Ubiquitin-Dependent Mitophagy: PINK1/Parkin Pathway. In defective mitochondria, PINK1 accumulates on the outer mitochondrial membrane (OMM), recruiting and activating Parkin, which ubiquitinates OMM proteins. LC3 adaptor proteins (e.g., P62, OPTN, NDP52) bind to these ubiquitinated proteins via UBD motifs and interact with LC3 through LIR motifs, facilitating the engulfment of damaged mitochondria. (B) Ubiquitin-Independent Mitophagy. This type of mitophagy involves specific mitochondrial membrane protein receptors like Nix/BNIP3L, BNIP3, and FUNDC1. These receptors directly bind to LC3 via their LIR motifs, acting as LC3 receptors. (C) Common Mitophagy Process. Both mechanisms involve the release of “eat me” signals from defective mitochondria. LC3 guides the mitochondria to be engulfed by double-membrane autophagosomes, forming autophagosomes. These then fuse with lysosomes to form autolysosomes, where mitochondria are degraded by lysosomal hydrolases.