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Msp1 cooperates with the proteasome for extraction of arrested mitochondrial import intermediates

Basch, M; Wagner, M; Rolland, S; Carbonell, A; Zeng, R; Khosravi, S; Schmidt, A; ... Wagener, N; + view all (2020) Msp1 cooperates with the proteasome for extraction of arrested mitochondrial import intermediates. Molecular Biology of the Cell , 31 (8) pp. 753-767. 10.1091/mbc.E19-06-0329. Green open access

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Abstract

The mitochondrial AAA ATPase Msp1 is well known for extraction of mislocalized tail-anchored ER proteins from the mitochondrial outer membrane. Here, we analyzed the extraction of precursors blocking the import pore in the outer membrane. We demonstrate strong genetic interactions of Msp1 and the proteasome with components of the TOM complex, the main translocase in the outer membrane. Msp1 and the proteasome both contribute to the removal of arrested precursor proteins that specifically accumulate in these mutants. The proteasome activity is essential for the removal as proteasome inhibitors block extraction. Furthermore, the proteasomal subunit Rpn10 copurified with Msp1. The human Msp1 homologue has been implicated in neurodegenerative diseases, and we show that the lack of the Caenorhabditis elegans Msp1 homologue triggers an import stress response in the worm, which indicates a conserved role in metazoa. In summary, our results suggest a role of Msp1 as an adaptor for the proteasome that drives the extraction of arrested and mislocalized proteins at the mitochondrial outer membrane.

Type: Article
Title: Msp1 cooperates with the proteasome for extraction of arrested mitochondrial import intermediates
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1091/mbc.E19-06-0329
Publisher version: https://doi.org/10.1091/mbc.E19-06-0329
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10100713
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