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Dual role of USP 30 in controlling basal pexophagy and mitophagy
Author(s) -
Marcassa Elena,
Kallinos Andreas,
Jardine Jane,
RusilowiczJones Emma V,
Martinez Aitor,
Kuehl Sandra,
Islinger Markus,
Clague Michael J,
Urbé Sylvie
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201745595
Subject(s) - mitophagy , microbiology and biotechnology , dual (grammatical number) , basal (medicine) , autophagy , chemistry , biology , biochemistry , endocrinology , apoptosis , art , literature , insulin
USP 30 is an integral protein of the outer mitochondrial membrane that counteracts PINK 1 and Parkin‐dependent mitophagy following acute mitochondrial depolarisation. Here, we use two distinct mitophagy reporter systems to reveal tonic suppression by USP 30, of a PINK 1‐dependent component of basal mitophagy in cells lacking detectable Parkin. We propose that USP 30 acts upstream of PINK 1 through modulation of PINK 1‐substrate availability and thereby determines the potential for mitophagy initiation. We further show that a fraction of endogenous USP 30 is independently targeted to peroxisomes where it regulates basal pexophagy in a PINK 1‐ and Parkin‐independent manner. Thus, we reveal a critical role of USP 30 in the clearance of the two major sources of ROS in mammalian cells and in the regulation of both a PINK 1‐dependent and a PINK 1‐independent selective autophagy pathway.