Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response

Aryatara Shakya, Nicholas W. McKee, Matthew Dodson, Eli Chapman, Donna D. Zhang

Research output: Contribution to journalShort surveypeer-review

5 Scopus citations


The transcription factor Nrf2 was originally identified as a master regulator of redox homeostasis, as it governs the expression of a battery of genes involved in mitigating oxidative and electrophilic stress. However, the central role of Nrf2 in dictating multiple facets of the cellular stress response has defined the Nrf2 pathway as a general mediator of cell survival. Recent studies have indicated that Nrf2 regulates the expression of genes controlling ferroptosis, an iron-and lipid peroxidation-dependent form of cell death. While Nrf2 was initially thought to have anti-ferroptotic function primarily through regulation of the antioxidant response, accumulating evidence has indicated that Nrf2 also exerts anti-ferroptotic effects via regulation of key aspects of iron and lipid metabolism. In this review, we will explore the emerging role of Nrf2 in mediating iron homeostasis and lipid peroxidation, where several Nrf2 target genes have been identified that encode critical proteins involved in these pathways. A better understanding of the mechanistic relationship between Nrf2 and ferroptosis, including how genetic and/or pharmacological manipulation of Nrf2 affect the ferroptotic response, should facilitate the development of new therapies that can be used to treat ferroptosis-associated diseases.

Original languageEnglish (US)
Pages (from-to)165-175
Number of pages11
JournalMolecules and Cells
Issue number3
StatePublished - Mar 31 2023


  • Nrf2
  • cancer
  • ferroptosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response'. Together they form a unique fingerprint.

Cite this