FIG. 2.

Schematic illustrating the import and processing of PINK1 by functional mitochondria. A canonical N-terminal mitochondrial targeting sequence of PINK1 is recognized by the translocases of the outer mitochondrial membrane (TOM) and the inner mitochondrial membrane (TIM). Depending on the experimental system, the PINK1 kinase domain may be protected from externally applied proteases (a), or remain partially exposed outside the mitochondrion (b). Mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protein (PARL), and other mitochondrial peptidases appear to sequentially cleave the N-terminal domain, resulting in release of mature, processed PINK1 to the intermembrane space (a) or its retro-translocation to the cytosol (b).