Figure 4.

Schematic overview of PINK1/Parkin mediated mitophagy. PINK1 accumulates at the surface of damaged mitochondria when the constitutive degradation of PINK in the mitochondrial matrix is inhibited. Subsequent homodimerization of PINK1 on the OMM leads to autophosphorylation, which promotes its activation. Activated PINK1 phosphorylates ubiquitin to recruit parkin, an E3 ubiquitin ligase, to the mitochondrial membrane. PINK1 regulates the localization and activity of parkin through phosphorylation of both ubiquitin and the ubiquitin-like domain of parkin. This process leads to ubiquitination of mitochondrial proteins on the OMM that can then be bound by autophagic proteins, ultimately triggering the formation of autophagosomes that deliver the damaged mitochondria to lysosomes for degradation.