Dual role of USP30 in controlling basal pexophagy and mitophagy.

TitleDual role of USP30 in controlling basal pexophagy and mitophagy.
Publication TypeJournal Article
Year of Publication2018
AuthorsMarcassa, E, Kallinos, A, Jardine, J, Rusilowicz-Jones, EV, Martinez, A, Kuehl, S, Islinger, M, Clague, MJ, Urbé, S
JournalEMBO Rep
Volume19
Issue7
Date Published2018 07
ISSN1469-3178
KeywordsAutophagy, Cell Line, Humans, Mitochondria, Mitochondrial Proteins, Mitophagy, Peroxisomes, Protein Kinases, Reactive Oxygen Species, Thiolester Hydrolases, Ubiquitin-Protein Ligases
Abstract

USP30 is an integral protein of the outer mitochondrial membrane that counteracts PINK1 and Parkin-dependent mitophagy following acute mitochondrial depolarisation. Here, we use two distinct mitophagy reporter systems to reveal tonic suppression by USP30, of a PINK1-dependent component of basal mitophagy in cells lacking detectable Parkin. We propose that USP30 acts upstream of PINK1 through modulation of PINK1-substrate availability and thereby determines the potential for mitophagy initiation. We further show that a fraction of endogenous USP30 is independently targeted to peroxisomes where it regulates basal pexophagy in a PINK1- and Parkin-independent manner. Thus, we reveal a critical role of USP30 in the clearance of the two major sources of ROS in mammalian cells and in the regulation of both a PINK1-dependent and a PINK1-independent selective autophagy pathway.

DOI10.15252/embr.201745595
Alternate JournalEMBO Rep.
Citation Key10.15252/embr.201745595
PubMed ID29895712
PubMed Central IDPMC6030704
Grant ListMR/N00941X/1 / / Medical Research Council / United Kingdom