Dual role of USP30 in controlling basal pexophagy and mitophagy
Open accessAbstract
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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USP30 is involved in pexophagy, peroxisomes have a half-life of 1.5-2.5 days, and pexophagy can be regulated by metabolic state, suggesting a role for NAD+ in pexophagy regulation.
“In addition to a role in mitophagy, USP30 was recently demonstrated to be involved in the peroxisome-specific degradation process, pexophagy. Peroxisomes have a half-life of 1.5–2.5 days, though pexophagy can be regulated by the metabolic state of the cells. This suggests a role for NAD+ in pexophagy regulation (Marcassa et al., 2018).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Marcassa et al., 2018
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References 46 · Cited by 158
- Authors
- Marcassa, E., Kallinos, A., Jardine, J., Rusilowicz‐Jones, E. V., Martinez, A., Kuehl, S., Islinger, M., Clague, M. J., & Urbé, S.
- Affiliations
- University of Liverpool (GB)
- Heidelberg University (DE)
- Corresponding author
- Clague, Michael J
- Urbé, Sylvie
- ORCID
- Venue
- The EMBO Reports
- Published
- 2018-06-12
- Volume
- 19
- Issue
- 7
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC6030704
- OpenAlex
- W2807910244
- Cited by
- 158
- References
- 46
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 18 · 2023: 17 · 2022: 24 · 2021: 22 · 2020: 23 · 2019: 18 · 2018: 5
- FWCI
- 13.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- EMBO Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- RCUK | MRC | Medical Research Foundation (MR/N00941X/1)
- Parkinson's UK (H‐1502)
- Michael J Fox Foundation for Parkinson's Research (13063)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- USP30, pexophagy, mitophagy, PINK1, Parkin, selective autophagy, peroxisomes, mitochondrial depolarization, mitochondrial outer membrane
- MeSH terms
- PTEN-Induced Putative Kinase, Autophagy, Cell Line, Humans, Mitochondria, Protein Kinases, Thiolester Hydrolases, Reactive Oxygen Species, Peroxisomes, Mitochondrial Proteins, Ubiquitin-Protein Ligases, Mitophagy
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