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Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45
Mitochondria are double-membraned organelles playing essential metabolic and signaling functions. The mitochondrial proteome is under surveillance by two proteolysis systems: the ubiquitin–proteasome system degrades mitochondrial outer-membrane (MOM) proteins, and the AAA proteases maintain the prot...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748973/ https://www.ncbi.nlm.nih.gov/pubmed/29138251 http://dx.doi.org/10.1083/jcb.201702125 |
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author | Wu, Xi Li, Lanlan Jiang, Hui |
author_facet | Wu, Xi Li, Lanlan Jiang, Hui |
author_sort | Wu, Xi |
collection | PubMed |
description | Mitochondria are double-membraned organelles playing essential metabolic and signaling functions. The mitochondrial proteome is under surveillance by two proteolysis systems: the ubiquitin–proteasome system degrades mitochondrial outer-membrane (MOM) proteins, and the AAA proteases maintain the proteostasis of intramitochondrial compartments. We previously identified a Doa1–Cdc48(-Ufd1-Npl4) complex that retrogradely translocates ubiquitinated MOM proteins to the cytoplasm for degradation. In this study, we report the unexpected identification of MOM proteins whose degradation requires the Yme1(-Mgr1-Mgr3) i-AAA protease complex in mitochondrial inner membrane. Through immunoprecipitation and in vivo site-specific photo–cross-linking experiments, we show that both Yme1 adapters Mgr1 and Mgr3 recognize the intermembrane space (IMS) domains of the MOM substrates and facilitate their recruitment to Yme1 for proteolysis. We also provide evidence that the cytoplasmic domain of substrate can be dislocated into IMS by the ATPase activity of Yme1. Our findings indicate a proteolysis pathway monitoring MOM proteins from the IMS side and suggest that the MOM proteome is surveilled by mitochondrial and cytoplasmic quality control machineries in parallel. |
format | Online Article Text |
id | pubmed-5748973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57489732018-07-02 Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45 Wu, Xi Li, Lanlan Jiang, Hui J Cell Biol Research Articles Mitochondria are double-membraned organelles playing essential metabolic and signaling functions. The mitochondrial proteome is under surveillance by two proteolysis systems: the ubiquitin–proteasome system degrades mitochondrial outer-membrane (MOM) proteins, and the AAA proteases maintain the proteostasis of intramitochondrial compartments. We previously identified a Doa1–Cdc48(-Ufd1-Npl4) complex that retrogradely translocates ubiquitinated MOM proteins to the cytoplasm for degradation. In this study, we report the unexpected identification of MOM proteins whose degradation requires the Yme1(-Mgr1-Mgr3) i-AAA protease complex in mitochondrial inner membrane. Through immunoprecipitation and in vivo site-specific photo–cross-linking experiments, we show that both Yme1 adapters Mgr1 and Mgr3 recognize the intermembrane space (IMS) domains of the MOM substrates and facilitate their recruitment to Yme1 for proteolysis. We also provide evidence that the cytoplasmic domain of substrate can be dislocated into IMS by the ATPase activity of Yme1. Our findings indicate a proteolysis pathway monitoring MOM proteins from the IMS side and suggest that the MOM proteome is surveilled by mitochondrial and cytoplasmic quality control machineries in parallel. The Rockefeller University Press 2018-01-02 /pmc/articles/PMC5748973/ /pubmed/29138251 http://dx.doi.org/10.1083/jcb.201702125 Text en © 2018 Wu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 | Research Articles Wu, Xi Li, Lanlan Jiang, Hui Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45 |
title | Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45 |
title_full | Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45 |
title_fullStr | Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45 |
title_full_unstemmed | Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45 |
title_short | Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45 |
title_sort | mitochondrial inner-membrane protease yme1 degrades outer-membrane proteins tom22 and om45 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748973/ https://www.ncbi.nlm.nih.gov/pubmed/29138251 http://dx.doi.org/10.1083/jcb.201702125 |
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