FIGURE 1.

Mechanism of mitophagy regulation in mammals. (a) In the PINK/PARKIN pathway, upon mitochondrial impairment or loss of mitochondrial potential, PINK1 can phosphorylate various target proteins, such as ubiquitin. Then, PINK1 recruits Parkin, and Parkin can amplify the signal through ubiquitination of miyochondrial surface receptor proteins. Receptor proteins can recognize the ubiquitinated proteins, which promotes mitochondria to form autophagosomes and eventually degrade them. (b) In the FUNDC1/BNIP3/NIX pathway, LC3 can be recognized by receptor proteins of mitochondria to promote the complementation of phagophores, thus targeting the mitochondrion for mitophagy. Mitochondrial outer membrane proteins FUNDC1, BNIP3 or NIX bind to LC3-II through their cytoplasmic LIR motifs to promote selective clearance of mitochondria. Δψ_m, mitochondrial potential; ROS, reactive oxygen species; IR, ischemia/reperfusion; Toxins, poisons produced naturally by organisms.