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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Hauptverfasser: Marcassa, Elena (VerfasserIn) , Kallinos, Andreas (VerfasserIn) , Jardine, Jane (VerfasserIn) , Rusilowicz-Jones, Emma V (VerfasserIn) , Martinez, Aitor (VerfasserIn) , Kühl, Sandra (VerfasserIn) , Islinger, Markus (VerfasserIn) , Clague, Michael J (VerfasserIn) , Urbé, Sylvie (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: [1 July 2018]
In: EMBO reports
Year: 2018, Jahrgang: 19, Heft: 7
ISSN:1469-3178
DOI:10.15252/embr.201745595
Online-Zugang: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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Verfasserangaben:Elena Marcassa, Andreas Kallinos, Jane Jardine, Emma V. Rusilowicz-Jones, Aitor Martinez, Sandra Kuehl, Markus Islinger, Michael J Clague & Sylvie Urbé
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Zusammenfassung: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.
Beschreibung:Gesehen am 11.10.2019
Beschreibung:Online Resource
ISSN:1469-3178
DOI:10.15252/embr.201745595