Parkin, an E3 ubiquitin ligase mutated in Parkinson's disease, induces mitophagy, the selective elimination of damaged mitochondria, by ubiquitinating and degrading mitofusins Mfn1 and Mfn2. This process is dependent on the proteasome and the AAA+ ATPase p97. Upon mitochondrial depolarization, Parkin prevents or delays refusion of mitochondria by eliminating mitofusins, likely through a mechanism involving p97 accumulation on mitochondria. Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy. These findings suggest that Parkin-mediated mitophagy involves the manipulation of mitochondrial dynamics and highlights the role of mitofusin degradation in mitophagy.Parkin, an E3 ubiquitin ligase mutated in Parkinson's disease, induces mitophagy, the selective elimination of damaged mitochondria, by ubiquitinating and degrading mitofusins Mfn1 and Mfn2. This process is dependent on the proteasome and the AAA+ ATPase p97. Upon mitochondrial depolarization, Parkin prevents or delays refusion of mitochondria by eliminating mitofusins, likely through a mechanism involving p97 accumulation on mitochondria. Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy. These findings suggest that Parkin-mediated mitophagy involves the manipulation of mitochondrial dynamics and highlights the role of mitofusin degradation in mitophagy.