Gerber, Markus; Suppanz, Ida; Oeljeklaus, Silke; Niemann, Moritz; Käser, Sandro; Warscheid, Bettina; Schneider, André; Dewar, Caroline E (2023). A Msp1-containing complex removes orphaned proteins in the mitochondrial outer membrane of T. brucei. Life science alliance, 6(11) EMBO Press 10.26508/lsa.202302004
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The AAA-ATPase Msp1 extracts mislocalised outer membrane proteins and thus contributes to mitochondrial proteostasis. Using pulldown experiments, we show that trypanosomal Msp1 localises to both glycosomes and the mitochondrial outer membrane, where it forms a complex with four outer membrane proteins. The trypanosome-specific pATOM36 mediates complex assembly of α-helically anchored mitochondrial outer membrane proteins such as protein translocase subunits. Inhibition of their assembly triggers a pathway that results in the proteasomal digestion of unassembled substrates. Using inducible single, double, and triple RNAi cell lines combined with proteomic analyses, we demonstrate that not only Msp1 but also the trypanosomal homolog of the AAA-ATPase VCP are implicated in this quality control pathway. Moreover, in the absence of VCP three out of the four Msp1-interacting mitochondrial proteins are required for efficient proteasomal digestion of pATOM36 substrates, suggesting they act in concert with Msp1. pATOM36 is a functional analog of the yeast mitochondrial import complex complex and possibly of human mitochondrial animal-specific carrier homolog 2, suggesting that similar mitochondrial quality control pathways linked to Msp1 might also exist in yeast and humans.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Gerber, Markus Daniel, Niemann, Moritz, Käser, Sandro, Schneider, André, Dewar, Caroline Elizabeth |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
2575-1077 |
Publisher: |
EMBO Press |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
17 Aug 2023 10:30 |
Last Modified: |
06 Feb 2024 07:22 |
Publisher DOI: |
10.26508/lsa.202302004 |
PubMed ID: |
37586887 |
BORIS DOI: |
10.48350/185522 |
URI: |
https://boris.unibe.ch/id/eprint/185522 |
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