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The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover

Recent studies have revealed a role for the ubiquitin/proteasome system in the regulation and turnover of outer mitochondrial membrane (OMM)-associated proteins. Although several molecular components required for this process have been identified, the mechanism of proteasome-dependent degradation of...

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Autores principales: Xu, Shan, Peng, Guihong, Wang, Yang, Fang, Shengyun, Karbowski, Mariusz
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031461/
https://www.ncbi.nlm.nih.gov/pubmed/21118995
http://dx.doi.org/10.1091/mbc.E10-09-0748
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author Xu, Shan
Peng, Guihong
Wang, Yang
Fang, Shengyun
Karbowski, Mariusz
author_facet Xu, Shan
Peng, Guihong
Wang, Yang
Fang, Shengyun
Karbowski, Mariusz
author_sort Xu, Shan
collection PubMed
description Recent studies have revealed a role for the ubiquitin/proteasome system in the regulation and turnover of outer mitochondrial membrane (OMM)-associated proteins. Although several molecular components required for this process have been identified, the mechanism of proteasome-dependent degradation of OMM-associated proteins is currently unclear. We show that an AAA-ATPase, p97, is required for the proteasomal degradation of Mcl1 and Mfn1, two unrelated OMM proteins with short half-lives. A number of biochemical assays, as well as imaging of changes in localization of photoactivable GFP-fused Mcl1, revealed that p97 regulates the retrotranslocation of Mcl1 from mitochondria to the cytosol, prior to, or concurrent with, proteasomal degradation. Mcl1 retrotranslocation from the OMM depends on the activity of the ATPase domain of p97. Furthermore, p97-mediated retrotranslocation of Mcl1 can be recapitulated in vitro, confirming a direct mitochondrial role for p97. Our results establish p97 as a novel and essential component of the OMM-associated protein degradation pathway.
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spelling pubmed-30314612011-04-16 The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover Xu, Shan Peng, Guihong Wang, Yang Fang, Shengyun Karbowski, Mariusz Mol Biol Cell Articles Recent studies have revealed a role for the ubiquitin/proteasome system in the regulation and turnover of outer mitochondrial membrane (OMM)-associated proteins. Although several molecular components required for this process have been identified, the mechanism of proteasome-dependent degradation of OMM-associated proteins is currently unclear. We show that an AAA-ATPase, p97, is required for the proteasomal degradation of Mcl1 and Mfn1, two unrelated OMM proteins with short half-lives. A number of biochemical assays, as well as imaging of changes in localization of photoactivable GFP-fused Mcl1, revealed that p97 regulates the retrotranslocation of Mcl1 from mitochondria to the cytosol, prior to, or concurrent with, proteasomal degradation. Mcl1 retrotranslocation from the OMM depends on the activity of the ATPase domain of p97. Furthermore, p97-mediated retrotranslocation of Mcl1 can be recapitulated in vitro, confirming a direct mitochondrial role for p97. Our results establish p97 as a novel and essential component of the OMM-associated protein degradation pathway. The American Society for Cell Biology 2011-02-01 /pmc/articles/PMC3031461/ /pubmed/21118995 http://dx.doi.org/10.1091/mbc.E10-09-0748 Text en © 2011 Xu et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Xu, Shan
Peng, Guihong
Wang, Yang
Fang, Shengyun
Karbowski, Mariusz
The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover
title The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover
title_full The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover
title_fullStr The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover
title_full_unstemmed The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover
title_short The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover
title_sort aaa-atpase p97 is essential for outer mitochondrial membrane protein turnover
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031461/
https://www.ncbi.nlm.nih.gov/pubmed/21118995
http://dx.doi.org/10.1091/mbc.E10-09-0748
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