Msp1 cooperates with the proteasome for extraction of arrested mitochondrial import intermediates
| Autor: | Nikola Wagener, Johannes Wagener, Wasim Aftab, Axel Imhof, Andres Carbonell, Marion Basch, Mirjam Wagner, Rachel Zeng, Stéphane G. Rolland, Siavash Khosravi, Andreas Schmidt, Barbara Conradt |
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| Rok vydání: | 2020 |
| Předmět: |
Cell Physiology
Proteasome Endopeptidase Complex Receptor complex Gene Expression TIM/TOM complex Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Tandem Mass Spectrometry Mitochondrial Precursor Protein Import Complex Proteins Protein Interaction Mapping parasitic diseases Animals Translocase Protein Precursors Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology 030304 developmental biology 0303 health sciences biology Membrane Proteins Membrane Transport Proteins Biological Transport Articles Cell Biology biology.organism_classification Recombinant Proteins AAA proteins Mitochondria Cell biology Proteasome Unfolded Protein Response biology.protein ATPases Associated with Diverse Cellular Activities Carrier Proteins Bacterial outer membrane Intermembrane space 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e19-06-0329 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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