PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. PINK1 expression on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels on healthy mitochondria while facilitating rapid accumulation on damaged ones. PINK1 accumulation is necessary and sufficient for Parkin recruitment, and disease-causing mutations in PINK1 and Parkin disrupt this process at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila. They also support a novel model for the negative selection of damaged mitochondria, where PINK1 signals mitochondrial dysfunction to Parkin, which then promotes their elimination. PINK1 accumulates on depolarized mitochondria, and its accumulation is inhibited by loss of membrane potential, leading to its stabilization on the outer mitochondrial membrane. PINK1 cleavage is voltage-dependent and proteasome-independent, followed by rapid degradation by the proteasome. PINK1 expression is required for Parkin recruitment to depolarized mitochondria and Parkin-induced mitophagy. PINK1 accumulation on depolarized mitochondria is independent of Parkin expression. Stable expression of PINK1 on the outer mitochondrial membrane is sufficient for Parkin recruitment and mitophagy. Patient mutations in PINK1 and Parkin disrupt the PINK1/Parkin pathway at distinct steps.PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. PINK1 expression on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels on healthy mitochondria while facilitating rapid accumulation on damaged ones. PINK1 accumulation is necessary and sufficient for Parkin recruitment, and disease-causing mutations in PINK1 and Parkin disrupt this process at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila. They also support a novel model for the negative selection of damaged mitochondria, where PINK1 signals mitochondrial dysfunction to Parkin, which then promotes their elimination. PINK1 accumulates on depolarized mitochondria, and its accumulation is inhibited by loss of membrane potential, leading to its stabilization on the outer mitochondrial membrane. PINK1 cleavage is voltage-dependent and proteasome-independent, followed by rapid degradation by the proteasome. PINK1 expression is required for Parkin recruitment to depolarized mitochondria and Parkin-induced mitophagy. PINK1 accumulation on depolarized mitochondria is independent of Parkin expression. Stable expression of PINK1 on the outer mitochondrial membrane is sufficient for Parkin recruitment and mitophagy. Patient mutations in PINK1 and Parkin disrupt the PINK1/Parkin pathway at distinct steps.