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USP 8 regulates mitophagy by removing K 6‐linked ubiquitin conjugates from parkin
Author(s) -
Durcan Thomas M,
Tang Matthew Y,
Pérusse Joëlle R,
Dashti Eman A,
Aguileta Miguel A,
McLelland GianLuca,
Gros Priti,
Shaler Thomas A,
Faubert Denis,
Coulombe Benoit,
Fon Edward A
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201489729
Subject(s) - parkin , mitophagy , biology , ubiquitin , ubiquitin protein ligases , microbiology and biotechnology , ubiquitin ligase , genetics , autophagy , parkinson's disease , gene , apoptosis , medicine , disease
Mutations in the Park2 gene, encoding the E3 ubiquitin‐ligase parkin, are responsible for a familial form of Parkinson's disease ( PD ). Parkin‐mediated ubiquitination is critical for the efficient elimination of depolarized dysfunctional mitochondria by autophagy (mitophagy). As damaged mitochondria are a major source of toxic reactive oxygen species within the cell, this pathway is believed to be highly relevant to the pathogenesis of PD . Little is known about how parkin‐mediated ubiquitination is regulated during mitophagy or about the nature of the ubiquitin conjugates involved. We report here that USP 8/ UBPY , a deubiquitinating enzyme not previously implicated in mitochondrial quality control, is critical for parkin‐mediated mitophagy. USP 8 preferentially removes non‐canonical K6‐linked ubiquitin chains from parkin, a process required for the efficient recruitment of parkin to depolarized mitochondria and for their subsequent elimination by mitophagy. This work uncovers a novel role for USP 8‐mediated deubiquitination of K6‐linked ubiquitin conjugates from parkin in mitochondrial quality control.