USP30 sets a trigger threshold for PINK1-PARKIN amplification of mitochondrial ubiquitylation.

ABSTRACT: The mitochondrial deubiquitylase USP30 negatively regulates the selective autophagy of damaged mitochondria. We present the characterisation of an N-cyano pyrrolidine compound, FT3967385, with high selectivity for USP30. We demonstrate that ubiquitylation of TOM20, a component of the outer mitochondrial membrane import machinery, represents a robust biomarker for both USP30 loss and inhibition. A proteomics analysis, on a SHSY5Y neuroblastoma cell line model, directly compares the effects of genetic loss of USP30 with chemical inhibition. We have thereby identified a subset of ubiquitylation events consequent to mitochondrial depolarisation that are USP30 sensitive. Within responsive elements of the ubiquitylome, several components of the outer mitochondrial membrane transport (TOM) comple

SUBMITTER: Rusilowicz-Jones EV 

PROVIDER: S-EPMC7362391 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature