Parkin-catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation

Abstract

Background: Parkin is a ubiquitin ligase activated by a decrease in the mitochondrial membrane potential (Δ Φm). However, details regarding its mechanism remain limited. Results: PINK1-dependent phosphorylation of Parkin at Ser-65 following dissipation of Δ Φm triggers ubiquitin-ester transfer by the RING2 domain of Parkin to Cys-431. Conclusion: Parkin catalyzes trans- (ubiquitin-thioester)ification upon PINK1-dependent phosphorylation. Significance: The molecular process of Parkin-catalyzed ubiquitylation has been determined. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.