Figure 8
From: Mdm2 enhances ligase activity of parkin and facilitates mitophagy
Mdm2 activates parkin and facilitates mitophagy. (A) PINK1 is degraded upon binding to healthy mitochondria. (B) Upon binding to mitochondria that lost their membrane potential PINK1 is no longer degraded but accumulates on the outer mitochondrial membrane (OMM). It phosphorylates ubiquitin at Ser65. Mitofusin1 (Mfn-1) is a resident protein in OMM in mitochondria. (C) Both parkin (PK) and Mdm2 are recruited independently of each other to the mitochondria that lost their membrane potential, although Mdm2 facilitates parkin recruitment. (D) PINK1 phosphorylates parkin at Ser-65 in the Ubiquitin-like domain homologous to Ser-65 of ubiquitin. Parkin activated by its phosphorylation, phospho-ubiquitin, and Mdm2 effectively ubiquitinates the OMM proteins including mitofusin1. This leads to degradation of OMM proteins and subsequent mitophagy.
