Proposed model of posttranslational processing of PINK1. Upper: newly synthesized PINK1 (p63) is targeted to the mitochondrial inner membrane (IM) via the Tom and Tim complexes. Full-length PINK1 is processed by mitochondrial processing protease (MPP), which cleaves the mitochondrial targeting sequence to generate the 60 kD form of PINK1 [130, 156]. PINK1 is then cleaved to a 52 kD form within the IM by PARL [68–71, 156]. The 52 kD PINK1 is released from the cytosol and degraded through proteasome activity. Lower: upon a decrease in Δψm, PINK1 is accumulated at the OM, most likely due to the inhibition of its transportation to the Tim complex.