Molecules and Cells

  • 제46권3호
  • /
  • Pages.165-175
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  • 2023
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response

  • Aryatara Shakya (Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona) ;
  • Nicholas W. McKee (Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona) ;
  • Matthew Dodson (Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona) ;
  • Eli Chapman (Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona) ;
  • Donna D. Zhang (Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona)
  • 투고 : 2023.01.02
  • 심사 : 2023.02.09
  • 발행 : 2023.03.31
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초록

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.

키워드

과제정보

D.D.Z. is supported by the following grants from the National Institutes of Health: R35ES031575 and P42ES004940.

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