(A) The PINK1 protein is composed of a regulatory region, consisting of the MTS, OMS and TMS, a catalytic KD and a C-terminal region which aids in substrate recognition. The exact location and length of the MTS is still debated, indicated by the shading. Also indicated are potential MPP cleavage sites, as well as the PARL cleavage site and phosphorylated serines. (B) Processing of PINK1 in healthy mitochondria. (1) PINK1 is imported into the mitochondria through the TOM/TIM complex owing to its N-terminal MTS. Cleavage by (2) MPP in the mitochondrial matrix, and (3) PARL on the IMM precede the release of cPINK1 into the cytosol (4). (5) Cytosolic PINK1 can be stabilised by chaperones or ubiquitination by TRAF6 before proteasomal degradation. Abbreviations: cPINK1, cleaved PINK1; PARL, presenilin-associated rhomboid-like protein.