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Dual role of USP30 in controlling basal pexophagy and mitophagy.

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.

SUBMITTER: Marcassa E

PROVIDER: S-EPMC6030704 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Dual role of USP30 in controlling basal pexophagy and mitophagy.

Marcassa Elena E Kallinos Andreas A Jardine Jane J Rusilowicz-Jones Emma V EV Martinez Aitor A Kuehl Sandra S Islinger Markus M Clague Michael J MJ Urbé Sylvie S

EMBO reports 20180612 7

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. ...[more]

PMID: 29895712

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