Fig. 1

Mechanism of mitophagy regulation in mammals (A, C) and yeasts (B). A Mitophagy receptors mediate mitophagy under hypoxia or starvation in mammals. The proteins BNIP3, BNIP3L, FKBP8 and FUNDC1 on the outer member of mitochondria directly bind with LC3 through their LIR domains. Lipid CL externalizes from the inner mitochondrial membrane and interacts with LC3 to initiate mitophagy. B Atg proteins mediated mitophagy in yeasts. Under nitrogen starvation, the mitochondrial outer member receptor Atg32 is phosphorylated by CK2 and interacts with Atg8 or Atg11 to promote mitophagy. C PINK1/Parkin-mediated mitophagy under mitochondrial depolarization in mammals. Mitochondrial stress blocks the internalization of PINK1. Accumulated PINK1 on the outer member of mitochondria recruits cytosolic Parkin to mitochondria and phosphorylates them. Then, the activated Parkin ubiquitinates the mitochondria outer member proteins such as Mfn1/Mfn2. Adaptors containing LIR motifs (e.g., p62, OPTN, NBR1) recognize these polyubiquitinated proteins and connect to autophagosomes via LC3