Figure 1.

The overview of mitophagy pathway. PRKN-dependent mitophagy. The phosphorylated PINK1 accumulates on the OMM when mitochondria are depolarized under various cellular stress and subsequently recruits PRKN to mitochondria. The E3 ligase PRKN polyubiquitinates multiple OMM proteins, which will be recognized by LC3 receptors including CALCOCO2, OPTN, and SQSTM1 on the phagophore. PRKN-independent mitophagy. The PRKN-mediated ubiquitylation of MFN also promotes mitochondria accessible for degradation and prevents fusion of damaged mitochondria. Alternatively, FUNDC1, BNIP3 and BNIP3L could directly bind the LC3 molecules decorating the autophagosome. Dephosphorylation of FUNDC1 enhances mitochondrial fission by the disassembly of OPA1, and increasing the interaction with DNM1L on the mitochondrial surface. Impaired mitochondria are engulfed by phagophores to form mitophagosomes, followed by the fusion with lysosomes to form mitolysosomes that degrades damaged mitochondria