Fig. 3

An overview of signaling nexus of mitophagy pathways. Dysfunctional mitochondria lose their membrane potential and are removed by mitophagy. A fission protein DRP1 is translocated to a dysfunctional mitochondrion and segregate it from healthy mitochondria. Then, potent mitophagy adaptor proteins BNIP3 and FUNDC1 locate to the isolated mitochondrion in which PINK1 (PTEN-induced putative kinase 1) accumulates and recruits a E3 ligase Parkin; in this process, another a E3 ligase MUL1 translocates to the mitochondrion. Parkin and MUL1 initiate ubiquitination of mitochondrial proteins, which are linked with LC3-II through a p62 ubiquitin binding motif and a LC3 interacting region and trapped inside of autophagosomes. Additionally, the LC3 interacting region of BNIP3 and FUNDC1 on the dysfunctional mitochondrial outer membrane binds to LC3 on the luminal side of an autophagosome and delivers the targeted mitochondria into the autophagosome. The delivered mitochondria are discarded through a lysosome. mPTP: Mitochondrial permeability transition pore