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An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion

Mitochondrial integrity relies on homotypic fusion between adjacent outer membranes, which is mediated by large GTPases called mitofusins. The regulation of this process remains nonetheless elusive. Here, we report a crosstalk between the ubiquitin protease Ubp2 and the ubiquitin ligases Mdm30 and R...

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Autores principales: Cavellini, Laetitia, Meurisse, Julie, Findinier, Justin, Erpapazoglou, Zoi, Belgareh-Touzé, Naïma, Weissman, Allan M., Cohen, Mickael M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474747/
https://www.ncbi.nlm.nih.gov/pubmed/28607491
http://dx.doi.org/10.1038/ncomms15832
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author Cavellini, Laetitia
Meurisse, Julie
Findinier, Justin
Erpapazoglou, Zoi
Belgareh-Touzé, Naïma
Weissman, Allan M.
Cohen, Mickael M.
author_facet Cavellini, Laetitia
Meurisse, Julie
Findinier, Justin
Erpapazoglou, Zoi
Belgareh-Touzé, Naïma
Weissman, Allan M.
Cohen, Mickael M.
author_sort Cavellini, Laetitia
collection PubMed
description Mitochondrial integrity relies on homotypic fusion between adjacent outer membranes, which is mediated by large GTPases called mitofusins. The regulation of this process remains nonetheless elusive. Here, we report a crosstalk between the ubiquitin protease Ubp2 and the ubiquitin ligases Mdm30 and Rsp5 that modulates mitochondrial fusion. Ubp2 is an antagonist of Rsp5, which promotes synthesis of the fatty acids desaturase Ole1. We show that Ubp2 also counteracts Mdm30-mediated turnover of the yeast mitofusin Fzo1 and that Mdm30 targets Ubp2 for degradation thereby inducing Rsp5-mediated desaturation of fatty acids. Exogenous desaturated fatty acids inhibit Ubp2 degradation resulting in higher levels of Fzo1 and maintenance of efficient mitochondrial fusion. Our results demonstrate that the Mdm30-Ubp2-Rsp5 crosstalk regulates mitochondrial fusion by coordinating an intricate balance between Fzo1 turnover and the status of fatty acids saturation. This pathway may link outer membrane fusion to lipids homeostasis.
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spelling pubmed-54747472017-07-03 An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion Cavellini, Laetitia Meurisse, Julie Findinier, Justin Erpapazoglou, Zoi Belgareh-Touzé, Naïma Weissman, Allan M. Cohen, Mickael M. Nat Commun Article Mitochondrial integrity relies on homotypic fusion between adjacent outer membranes, which is mediated by large GTPases called mitofusins. The regulation of this process remains nonetheless elusive. Here, we report a crosstalk between the ubiquitin protease Ubp2 and the ubiquitin ligases Mdm30 and Rsp5 that modulates mitochondrial fusion. Ubp2 is an antagonist of Rsp5, which promotes synthesis of the fatty acids desaturase Ole1. We show that Ubp2 also counteracts Mdm30-mediated turnover of the yeast mitofusin Fzo1 and that Mdm30 targets Ubp2 for degradation thereby inducing Rsp5-mediated desaturation of fatty acids. Exogenous desaturated fatty acids inhibit Ubp2 degradation resulting in higher levels of Fzo1 and maintenance of efficient mitochondrial fusion. Our results demonstrate that the Mdm30-Ubp2-Rsp5 crosstalk regulates mitochondrial fusion by coordinating an intricate balance between Fzo1 turnover and the status of fatty acids saturation. This pathway may link outer membrane fusion to lipids homeostasis. Nature Publishing Group 2017-06-13 /pmc/articles/PMC5474747/ /pubmed/28607491 http://dx.doi.org/10.1038/ncomms15832 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Cavellini, Laetitia
Meurisse, Julie
Findinier, Justin
Erpapazoglou, Zoi
Belgareh-Touzé, Naïma
Weissman, Allan M.
Cohen, Mickael M.
An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
title An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
title_full An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
title_fullStr An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
title_full_unstemmed An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
title_short An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
title_sort ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474747/
https://www.ncbi.nlm.nih.gov/pubmed/28607491
http://dx.doi.org/10.1038/ncomms15832
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