Journal
EMBO REPORTS
Volume 19, Issue 7, Pages -Publisher
WILEY
DOI: 10.15252/embr.201745595
Keywords
mitochondria; peroxisomes; PINK1; ubiquitin; mitophagy; USP30
Categories
Funding
- Medical Research Council [MR/N00941X/1]
- Parkinson's UK studentship [H-1502]
- Michael J Fox Foundation Therapeutic Pipeline project [13063]
- MRC [MR/N00941X/1] Funding Source: UKRI
- Medical Research Council [MR/N00941X/1] Funding Source: researchfish
- Parkinson's UK [H-1502] Funding Source: researchfish
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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.
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