Knockout of the ubiquitin ligase Parkin, the gene product of the Parkinson associated Park2, leads to loss of mitochondrial integrity and function in Drosophila melanogaster. Although Parkin is primarily cytosolic, we have found that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential and subsequently promotes their autophagy. Here we report that Parkin recruitment is voltage-dependent and independent of changes in ATP or pH. These findings suggest that Parkin promotes mitophagy of dysfunctional mitochondria following loss of mitochondrial membrane potential and implicate the targeted elimination of mitochondria in the pathogenesis of Parkinson disease.
D Narendra, A Tanaka, DF Suen, RJ Youle. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183: 795- 803.
PMID: 19029340 DOI: 10.1083/jcb.20080912