Damaged or senescent mitochondria are removed by mitophagy, an organelle quality control mechanism that, if disrupted, causes degenerative disease. The serine–threonine kinase PINK1 directs the E3 ubiquitin ligase Parkin to damaged mitochondria to promote their elimination, but exactly how Parkin is targeted to mitochondria has been unknown.

Now Chen and Dorn (Science 340, 471–475; 2013) have identified the mitochondrial receptor for Parkin. They focused on mitofusins (Mfn), known substrates for Parkin ubiquitylation. Mfn2, but not Mfn1, was shown to bind Parkin and mediate its recruitment to mitochondria. In the absence of Mfn2 in cardiomyocytes, mitochondrial protein ubiquitylation was decreased after mitophagic stimulation. PINK1 was shown to enhance the interaction between Mfn2 and Parkin, owing to its ability to phosphorylate Mfn2. Deletion of Mfn2, but not Mfn1, in cardiomyocytes caused mitochondrial enlargement and respiratory impairment. In mice, cardiomyocyte-specific deletion of Mfn2 led to dilatation of the ageing hearts and impaired contractile performance. Cardiomyocytes and heart tubes of Parkin-deficient flies recapitulated the phenotype of the cardiac-specific Mfn2-deficient mice, indicating that in both models the impairment in ubiquitylation of damaged mitochondrial proteins contributes to accumulation of abnormal mitochondria that impede cellular respiration and cardiac function.