The Nrf2 regulatory network provides an interface between redox and intermediary metabolism

John D. Hayes (Lead / Corresponding author), Albena T. Dinkova-Kostova

    Research output: Contribution to journalArticle

    718 Citations (Scopus)

    Abstract

    Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2) is a transcription factor that regulates the cellular redox status. Nrf2 is controlled through a complex transcriptional/epigenetic and post-translational network that ensures its activity increases during redox perturbation, inflammation, growth factor stimulation and nutrient/energy fluxes, thereby enabling the factor to orchestrate adaptive responses to diverse forms of stress. Besides mediating stress-stimulated induction of antioxidant and detoxification genes, Nrf2 contributes to adaptation by upregulating the repair and degradation of damaged macromolecules, and by modulating intermediary metabolism. In the latter case, Nrf2 inhibits lipogenesis, supports ß-oxidation of fatty acids, facilitates flux through the pentose phosphate pathway, and increases NADPH regeneration and purine biosynthesis; these observations suggest Nrf2 directs metabolic reprogramming during stress.
    Original languageEnglish
    Pages (from-to)199-218
    Number of pages20
    JournalTrends in Biochemical Sciences
    Volume39
    Issue number4
    DOIs
    Publication statusPublished - Apr 2014

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