Figure 1

Parkin recruitment to depolarized mitochondria promotes their degradation by mitophagy. In polarized mitochondria, PINK1 is degraded in the mitochondrial matrix (left), but upon membrane depolarization, PINK1 is stabilized and accumulates at the OMM, where it phosphorylates Mfn-2 and other substrates, including ubiquitin, that act as receptors for Parkin. Once Parkin is recruited to the OMM, it ubiquitinates key protein substrates including VDAC1 and Mfn-2, and other possibly unknown targets (substrate X). Parkin-dependent ubiquitination of VDAC1 and other mitochondrial proteins promotes interaction with p62/Sqstm1 that in turn facilitates interaction with LC3 at nascent phagophores thereby targeting depolarized mitochondria for degradation by autophagy.