000070893 001__ 70893 000070893 005__ 20191122145054.0 000070893 0247_ $$2doi$$a10.1038/s41598-018-23884-4 000070893 0248_ $$2sideral$$a106369 000070893 037__ $$aART-2018-106369 000070893 041__ $$aeng 000070893 100__ $$aKhan, A.U.H. 000070893 245__ $$aMitochondrial complex I activity signals antioxidant response through ERK5 000070893 260__ $$c2018 000070893 5060_ $$aAccess copy available to the general public$$fUnrestricted 000070893 5203_ $$aOxidative 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. 000070893 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000070893 590__ $$a4.011$$b2018 000070893 591__ $$aMULTIDISCIPLINARY SCIENCES$$b14 / 69 = 0.203$$c2018$$dQ1$$eT1 000070893 592__ $$a1.414$$b2018 000070893 593__ $$aMultidisciplinary$$c2018$$dQ1 000070893 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000070893 700__ $$aAllende-Vega, N. 000070893 700__ $$aGitenay, D. 000070893 700__ $$aGaraude, J. 000070893 700__ $$aVo, D.-N. 000070893 700__ $$aBelkhala, S. 000070893 700__ $$aGerbal-Chaloin, S. 000070893 700__ $$aGondeau, C. 000070893 700__ $$aDaujat-Chavanieu, M. 000070893 700__ $$aDelettre, C. 000070893 700__ $$aOrecchioni, S. 000070893 700__ $$aTalarico, G. 000070893 700__ $$aBertolini, F. 000070893 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza 000070893 700__ $$aCuezva, J.M. 000070893 700__ $$aEnriquez, J.A. 000070893 700__ $$aCartron, G. 000070893 700__ $$aLecellier, C.-H. 000070893 700__ $$aHernandez, J. 000070893 700__ $$aVillalba, M. 000070893 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000070893 773__ $$g8, 1 (2018), 7420 [14 pp]$$pSci. rep.$$tSCIENTIFIC REPORTS$$x2045-2322 000070893 8564_ $$s2229084$$uhttps://zaguan.unizar.es/record/70893/files/texto_completo.pdf$$yVersión publicada 000070893 8564_ $$s117741$$uhttps://zaguan.unizar.es/record/70893/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000070893 909CO $$ooai:zaguan.unizar.es:70893$$particulos$$pdriver 000070893 951__ $$a2019-11-22-14:44:52 000070893 980__ $$aARTICLE