Nrf2 and AhR in metabolic reprogramming after contaminant exposure

Sylvie Bortoli (1) , Elisa Boutet-Robinet (2) , Dominique Lagadic-Gossmann (2) , Laurence Huc (3)

1 ToxAlim - ToxAlim
2 Irset - Institut de recherche en santé, environnement et travail
3 T3S - UMR_S 1124 - Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire

Beside their crucial role in xenobiotic biotransformation, AhR and Nrf2 are involved in the regulation of energetic metabolism. Nrf2, as a cytoprotective transcription factor, supply energy for detoxification and antioxidant response. AhR is ligand-activated transcriptional factor implicated in several physiological function. Following pollutant exposure, it acts as a chemosensor to eliminate harmful chemicals. Altogether, AhR and Nrf2 cooperate to contribute to protective responses upon contaminant exposure, including metabolic remodelling. This fine-tuned energetic coupling with detoxification can lead to prominent dysfunction under a chronic exposure to pollutants, and promote a long-term reprogramming that affects multiple cellular activities. In the article, we review the involvement of Nrf2 and AhR in the metabolic adaptations that occur during the short-term cell defence upon toxicant exposure, and in the metabolic reprogramming caused by their sustained activation. We also provide several clues to highlight the potential role of the Nrf2/AhR-induced metabolic changes in environmental carcinogenesis. © 2017

Keywords: Metabolic reprogramming; detoxification; AhR; environmental carcinogenesis; Nrf2

Domains: Life Sciences [q-bio]; Ecology, environment; Health

Sylvie Bortoli, Elisa Boutet-Robinet, Dominique Lagadic-Gossmann, Laurence Huc. Nrf2 and AhR in metabolic reprogramming after contaminant exposure. Current Opinion in Toxicology, 2018, 8, pp.34-41. ⟨10.1016/j.cotox.2017.12.001⟩. ⟨hal-01699380⟩