Dual role of USP 30 in controlling basal pexophagy and mitophagy



Marcassa, E, Kallinos, A ORCID: 0000-0001-8771-963X, Jardine, J ORCID: 0000-0002-7646-9636, Rusilowicz, Emma, Martinez, Aitor, Kuehl, Sandra, Islinger, Markus, Clague, Michael ORCID: 0000-0003-3355-9479 and Urbe, S ORCID: 0000-0003-4735-9814
(2018) Dual role of USP 30 in controlling basal pexophagy and mitophagy. EMBO Reports, 19 (07).

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: mitochondria, peroxisomes, PINK1, ubiquitin, mitophagy, USP30
Depositing User: Symplectic Admin
Date Deposited: 29 May 2018 06:54
Last Modified: 19 Jan 2023 01:33
DOI: 10.15252/embr.201745595
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3021772