PINK1

PINK1 (PTEN-induced kinase 1) is a mitochondrial serine/threonine kinase that serves as a sensor of mitochondrial damage. In healthy mitochondria with an intact membrane potential, PINK1 is imported into the inner membrane and rapidly cleaved by PARL and degraded. When the membrane potential collapses, import fails and PINK1 instead accumulates on the outer mitochondrial membrane, where it dimerizes and autophosphorylates. Active PINK1 phosphorylates ubiquitin and the E3 ligase Parkin at conserved Ser65 residues, recruiting and activating Parkin to drive ubiquitination of outer-membrane proteins and selective autophagy of the damaged mitochondrion (mitophagy). Loss-of-function mutations in PINK1 cause autosomal recessive early-onset Parkinson disease, and impaired PINK1-Parkin signaling has been implicated in age-associated mitochondrial dysfunction.