Mitochondrial Complex I activity signals antioxidant response through ERK5

Abstract Oxidative phosphorylation (OXPHOS) generates ROS as a byproduct of mitochondrial complex I activity. ROS-detoxifying enzymes are made available through the activation of their antioxidant response elements (ARE) in their gene promoters. NRF2 binds to AREs and induces this anti-oxidant respo...

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Autores principales:	Abrar Ul Haq Khan, Nerea Allende-Vega, Delphine Gitenay, Johan Garaude, Dang-Nghiem Vo, Sana Belkhala, Sabine Gerbal-Chaloin, Claire Gondeau, Martine Daujat-Chavanieu, Cécile Delettre, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Alberto Anel, José M. Cuezva, Jose A. Enriquez, Guillaume Cartron, Charles-Henri Lecellier, Javier Hernandez, Martin Villalba
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc2bb76d7c6941359df8d4c75d727c38
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spelling	oai:doaj.org-article:cc2bb76d7c6941359df8d4c75d727c382021-12-02T15:08:24ZMitochondrial Complex I activity signals antioxidant response through ERK510.1038/s41598-018-23884-42045-2322https://doaj.org/article/cc2bb76d7c6941359df8d4c75d727c382018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23884-4https://doaj.org/toc/2045-2322Abstract Oxidative phosphorylation (OXPHOS) generates ROS as a byproduct of mitochondrial complex I activity. ROS-detoxifying enzymes are made available through the activation of their antioxidant response elements (ARE) in their gene promoters. NRF2 binds to AREs and induces this anti-oxidant response. We show that cells from multiple origins performing OXPHOS induced NRF2 expression and its transcriptional activity. The NRF2 promoter contains MEF2 binding sites and the MAPK ERK5 induced MEF2-dependent NRF2 expression. Blocking OXPHOS in a mouse model decreased Erk5 and Nrf2 expression. Furthermore, fibroblasts derived from patients with mitochondrial disorders also showed low expression of ERK5 and NRF2 mRNAs. Notably, in cells lacking functional mitochondrial complex I activity OXPHOS did not induce ERK5 expression and failed to generate this anti-oxidant response. Complex I activity induces ERK5 expression through fumarate accumulation. Eukaryotic cells have evolved a genetic program to prevent oxidative stress directly linked to OXPHOS and not requiring ROS.Abrar Ul Haq KhanNerea Allende-VegaDelphine GitenayJohan GaraudeDang-Nghiem VoSana BelkhalaSabine Gerbal-ChaloinClaire GondeauMartine Daujat-ChavanieuCécile DelettreStefania OrecchioniGiovanna TalaricoFrancesco BertoliniAlberto AnelJosé M. CuezvaJose A. EnriquezGuillaume CartronCharles-Henri LecellierJavier HernandezMartin VillalbaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abrar Ul Haq Khan Nerea Allende-Vega Delphine Gitenay Johan Garaude Dang-Nghiem Vo Sana Belkhala Sabine Gerbal-Chaloin Claire Gondeau Martine Daujat-Chavanieu Cécile Delettre Stefania Orecchioni Giovanna Talarico Francesco Bertolini Alberto Anel José M. Cuezva Jose A. Enriquez Guillaume Cartron Charles-Henri Lecellier Javier Hernandez Martin Villalba Mitochondrial Complex I activity signals antioxidant response through ERK5
description	Abstract Oxidative phosphorylation (OXPHOS) generates ROS as a byproduct of mitochondrial complex I activity. ROS-detoxifying enzymes are made available through the activation of their antioxidant response elements (ARE) in their gene promoters. NRF2 binds to AREs and induces this anti-oxidant response. We show that cells from multiple origins performing OXPHOS induced NRF2 expression and its transcriptional activity. The NRF2 promoter contains MEF2 binding sites and the MAPK ERK5 induced MEF2-dependent NRF2 expression. Blocking OXPHOS in a mouse model decreased Erk5 and Nrf2 expression. Furthermore, fibroblasts derived from patients with mitochondrial disorders also showed low expression of ERK5 and NRF2 mRNAs. Notably, in cells lacking functional mitochondrial complex I activity OXPHOS did not induce ERK5 expression and failed to generate this anti-oxidant response. Complex I activity induces ERK5 expression through fumarate accumulation. Eukaryotic cells have evolved a genetic program to prevent oxidative stress directly linked to OXPHOS and not requiring ROS.
format	article
author	Abrar Ul Haq Khan Nerea Allende-Vega Delphine Gitenay Johan Garaude Dang-Nghiem Vo Sana Belkhala Sabine Gerbal-Chaloin Claire Gondeau Martine Daujat-Chavanieu Cécile Delettre Stefania Orecchioni Giovanna Talarico Francesco Bertolini Alberto Anel José M. Cuezva Jose A. Enriquez Guillaume Cartron Charles-Henri Lecellier Javier Hernandez Martin Villalba
author_facet	Abrar Ul Haq Khan Nerea Allende-Vega Delphine Gitenay Johan Garaude Dang-Nghiem Vo Sana Belkhala Sabine Gerbal-Chaloin Claire Gondeau Martine Daujat-Chavanieu Cécile Delettre Stefania Orecchioni Giovanna Talarico Francesco Bertolini Alberto Anel José M. Cuezva Jose A. Enriquez Guillaume Cartron Charles-Henri Lecellier Javier Hernandez Martin Villalba
author_sort	Abrar Ul Haq Khan
title	Mitochondrial Complex I activity signals antioxidant response through ERK5
title_short	Mitochondrial Complex I activity signals antioxidant response through ERK5
title_full	Mitochondrial Complex I activity signals antioxidant response through ERK5
title_fullStr	Mitochondrial Complex I activity signals antioxidant response through ERK5
title_full_unstemmed	Mitochondrial Complex I activity signals antioxidant response through ERK5
title_sort	mitochondrial complex i activity signals antioxidant response through erk5
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/cc2bb76d7c6941359df8d4c75d727c38
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Mitochondrial Complex I activity signals antioxidant response through ERK5

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