FIGURE 4.

Activation of PINK1/Parkin-mediated mitophagy. PINK1 accumulates on the outer mitochondrial membrane (OMM) in the absence of ΔΨ. PINK1 recruits and activates Parkin in a process involving PINK1-mediated phosphorylation of Mfn2, ubiquitin (Ub), and Parkin. Activated Parkin conjugates ubiquitin to various proteins in the OMM. The ubiquitin chains on proteins in the OMM are recognized by autophagy adaptors which in turn tether the ubiquitinated cargo to the autophagosome via binding to lipidated LC3.