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

John D. Hayes, Albena T. Dinkova-Kostova

Research output: Contribution to journalArticlepeer-review

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 β-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 (US)
Pages (from-to)199-218
Number of pages20
JournalTrends in Biochemical Sciences
Volume39
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Fatty acid β-oxidation
  • Glutathione
  • GSK-3
  • Keap1
  • NADPH
  • Nrf2
  • Oxidative stress
  • Pentose phosphate pathway
  • Purine synthesis
  • Thioredoxin
  • β-TrCP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Medicine(all)

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