2026-05-22T17:28:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66712024-09-27T09:31:15Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Khan, Abrar Ul Haq
author
Allende-Vega, Nerea
author
Gitenay, Delphine
author
Garaude, Johan
author
Vo, Dang-Nghiem
author
Belkhala, Sana
author
Gerbal-Chaloin, Sabine
author
Gondeau, Claire
author
Daujat-Chavanieu, Martine
author
Delettre, Cecile
author
Orecchioni, Stefania
author
Talarico, Giovanna
author
Bertolini, Francesco
author
Anel, Alberto
author
Cuezva, Jose M.
author
Enriquez, Jose Antonio
author
Cartron, Guillaume
author
Lecellier, Charles-Henri
author
Hernandez, Javier
author
Villalba, Martin
funder
Region Languedoc Roussillon
funder
Higher Education Commission (Pakistan)
funder
Ministere de l'Enseignement Superieur et de la Recherche (Francia)
2018-11-22T08:10:51Z
2018-11-22T08:10:51Z
2018
Sci Rep. 2018; 8(1):7420
10.1038/s41598-018-23884-4
2045-2322
Scientific Reports
29743487
http://hdl.handle.net/20.500.12105/6671
Oxidative phosphorylation (OXPHOS) generates ROS as a by product 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.
eng
ACTIVATED PROTEIN-KINASE
NF-KAPPA-B
MHC CLASS-I
OXIDATIVE-PHOSPHORYLATION
GENE-EXPRESSION
CANCER-CELLS
NRF2
PATHWAY
STRESS
METABOLISM
Mitochondrial Complex I activity signals antioxidant response through ERK5
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