Senescent and damaged mitochondria undergo selective mitophagic elimination 
through mechanisms requiring two Parkinson's disease factors, the mitochondrial 
kinase PINK1 (PTEN-induced putative kinase protein 1; PTEN is phosphatase and 
tensin homolog) and the cytosolic ubiquitin ligase Parkin. The nature of the 
PINK-Parkin interaction and the identity of key factors directing Parkin to 
damaged mitochondria are unknown. We show that the mitochondrial outer membrane 
guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to 
damaged mitochondria. Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 
phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. Ablation of 
Mfn2 in mouse cardiac myocytes prevented depolarization-induced translocation of 
Parkin to the mitochondria and suppressed mitophagy. Accumulation of 
morphologically and functionally abnormal mitochondria induced respiratory 
dysfunction in Mfn2-deficient mouse embryonic fibroblasts and cardiomyocytes and 
in Parkin-deficient Drosophila heart tubes, causing dilated cardiomyopathy. 
Thus, Mfn2 functions as a mitochondrial receptor for Parkin and is required for 
quality control of cardiac mitochondria.