Figure 2.

1) Pink1 is sequentially targeted to the mitochondria via a targeting sequence and is degraded by the matrix processing peptidase (MPP) and subsequently cleaved by the IMM protease progerin-associated rhodopsin-like enzyme (PARL). Pink1 accumulates on the OMM via the regulation of the enzyme translocase of the outer membrane (TOM). Accumulated pink1 is autophosphorylated and activated through autophosphorylation which then phosphorylates ubiquitin on serine 65 (Ser65), triggering the recruitment of Parkin to the mitochondrial membrane. PINK1 and its substrate, ubiquitinates, phosphorylates and activates Parkin. Specifically, polyubiquitination of Parkin substrates, such as voltage-dependent anion channel-1 (VDAC1), mfn1/2, and Miro 1, induces their degradation by the proteasome. 2) Bcl2 like 13 (BCL2L13) is the mammalian homolog of atg32. In mammalian cells, BCL2L13 facilitates mitosis independently of Parkin. Like other LC3 receptors, BCL2L13 is located on the outer mitochondrial membrane and binds to LC3 via the LIR motif. Specifically, phosphorylation of the Ser272 site enhances the binding of BCL2L13 to the LC3.FK506-binding protein 8 (FKBP8). FKBP8 is located on the outer mitochondrial membrane and stimulates mitochondrial autophagy by interacting with LC3A; 3) Cardiolipin is an inner mitochondrial membrane lipid, and PHB2 are IMM proteins, which bind to the LC3 receptor to initiate mitophagy.