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EMBO Rep. 2018 Jun 12. pii: e45595. doi: 10.15252/embr.201745595. [Epub ahead of print]

Dual role of USP30 in controlling basal pexophagy and mitophagy.

Author information

1
Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
2
Institute of Neuroanatomy, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
3
Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK clague@liv.ac.uk urbe@liv.ac.uk.

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.

KEYWORDS:

PINK1; USP30; mitochondria; mitophagy; peroxisomes; ubiquitin

PMID:
29895712
DOI:
10.15252/embr.201745595
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