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 b...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[1 July 2018]
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| In: |
EMBO reports
Year: 2018, Volume: 19, Issue: 7 |
| ISSN: | 1469-3178 |
| DOI: | 10.15252/embr.201745595 |
| Online Access: | Verlag, Volltext: https://doi.org/10.15252/embr.201745595 Verlag, Volltext: https://www.embopress.org/doi/full/10.15252/embr.201745595 
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| Author Notes: | Elena Marcassa, Andreas Kallinos, Jane Jardine, Emma V. Rusilowicz-Jones, Aitor Martinez, Sandra Kuehl, Markus Islinger, Michael J Clague & Sylvie Urbé |
| Summary: | 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. |
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| Item Description: | Gesehen am 11.10.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1469-3178 |
| DOI: | 10.15252/embr.201745595 |