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A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis

Mitochondria critically rely on protein import and its tight regulation. Here, we found that the complex I assembly factor NDUFAF8 follows a two-step import pathway linking IMS and matrix import systems. A weak targeting sequence drives TIM23-dependent NDUFAF8 matrix import, and en route, allows exp...

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Autores principales: Peker, Esra, Weiss, Konstantin, Song, Jiyao, Zarges, Christine, Gerlich, Sarah, Boehm, Volker, Trifunovic, Aleksandra, Langer, Thomas, Gehring, Niels H., Becker, Thomas, Riemer, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174193/
https://www.ncbi.nlm.nih.gov/pubmed/37159021
http://dx.doi.org/10.1083/jcb.202210019
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author Peker, Esra
Weiss, Konstantin
Song, Jiyao
Zarges, Christine
Gerlich, Sarah
Boehm, Volker
Trifunovic, Aleksandra
Langer, Thomas
Gehring, Niels H.
Becker, Thomas
Riemer, Jan
author_facet Peker, Esra
Weiss, Konstantin
Song, Jiyao
Zarges, Christine
Gerlich, Sarah
Boehm, Volker
Trifunovic, Aleksandra
Langer, Thomas
Gehring, Niels H.
Becker, Thomas
Riemer, Jan
author_sort Peker, Esra
collection PubMed
description Mitochondria critically rely on protein import and its tight regulation. Here, we found that the complex I assembly factor NDUFAF8 follows a two-step import pathway linking IMS and matrix import systems. A weak targeting sequence drives TIM23-dependent NDUFAF8 matrix import, and en route, allows exposure to the IMS disulfide relay, which oxidizes NDUFAF8. Import is closely surveyed by proteases: YME1L prevents accumulation of excess NDUFAF8 in the IMS, while CLPP degrades reduced NDUFAF8 in the matrix. Therefore, NDUFAF8 can only fulfil its function in complex I biogenesis if both oxidation in the IMS and subsequent matrix import work efficiently. We propose that the two-step import pathway for NDUFAF8 allows integration of the activity of matrix complex I biogenesis pathways with the activity of the mitochondrial disulfide relay system in the IMS. Such coordination might not be limited to NDUFAF8 as we identified further proteins that can follow such a two-step import pathway.
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spelling pubmed-101741932023-11-09 A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis Peker, Esra Weiss, Konstantin Song, Jiyao Zarges, Christine Gerlich, Sarah Boehm, Volker Trifunovic, Aleksandra Langer, Thomas Gehring, Niels H. Becker, Thomas Riemer, Jan J Cell Biol Article Mitochondria critically rely on protein import and its tight regulation. Here, we found that the complex I assembly factor NDUFAF8 follows a two-step import pathway linking IMS and matrix import systems. A weak targeting sequence drives TIM23-dependent NDUFAF8 matrix import, and en route, allows exposure to the IMS disulfide relay, which oxidizes NDUFAF8. Import is closely surveyed by proteases: YME1L prevents accumulation of excess NDUFAF8 in the IMS, while CLPP degrades reduced NDUFAF8 in the matrix. Therefore, NDUFAF8 can only fulfil its function in complex I biogenesis if both oxidation in the IMS and subsequent matrix import work efficiently. We propose that the two-step import pathway for NDUFAF8 allows integration of the activity of matrix complex I biogenesis pathways with the activity of the mitochondrial disulfide relay system in the IMS. Such coordination might not be limited to NDUFAF8 as we identified further proteins that can follow such a two-step import pathway. Rockefeller University Press 2023-05-09 /pmc/articles/PMC10174193/ /pubmed/37159021 http://dx.doi.org/10.1083/jcb.202210019 Text en © 2023 Peker et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Peker, Esra
Weiss, Konstantin
Song, Jiyao
Zarges, Christine
Gerlich, Sarah
Boehm, Volker
Trifunovic, Aleksandra
Langer, Thomas
Gehring, Niels H.
Becker, Thomas
Riemer, Jan
A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis
title A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis
title_full A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis
title_fullStr A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis
title_full_unstemmed A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis
title_short A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis
title_sort two-step mitochondrial import pathway couples the disulfide relay with matrix complex i biogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174193/
https://www.ncbi.nlm.nih.gov/pubmed/37159021
http://dx.doi.org/10.1083/jcb.202210019
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