Figure 2.

Molecular mechanism of mitophagy. A decreased mitochondrial membrane potential increases membrane depolarization and accumulates PINK1 kinase at the OMM. PINK1 recruits PARK2 and targets it at the damaged mitochondria. The activation of PINK1/PARK2 in the OMM allows the interaction with LC3 for autophagic degradation through specific adaptor proteins, such as SQSTM1/p62, which binds simultaneously with ubiquitin and LC3 to drive the process. Mitophagy is also induced by mitochondrial receptors, such as BNIP3, NIX, FUNDC1, Bcl2-L-13, which directly bind LC3 through the conserved LC3-interacting region (LIR).