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Cited by 2,435Genomics, phytochemicals, and oxidative stressFerroptosis and cancer prognosisRedox biology and oxidative stress

NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis

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Dodson, Matthew, Castro-Portuguez, Raul, Zhang, Donna D.·2019·Redox Biology
DOI 10.1016/j.redox.2019.101107PMC PMC6859567
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Abstract

The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the cellular antioxidant response, controlling the expression of genes that counteract oxidative and electrophilic stresses. Many pathological conditions are linked to imbalances in redox homeostasis, illustrating the important role of antioxidant defense systems in preventing the pathogenic effects associated with the accumulation of reactive species. In particular, it is becoming increasingly apparent that the accumulation of lipid peroxides has an important role in driving the pathogenesis of multiple disease states. A key example of this is the recent discovery of a novel form of cell death termed ferroptosis. Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death cascade that has become a key target in the development of anti-cancer therapies, as well as the prevention of neurodegenerative and cardiovascular diseases. In this review, we will provide a brief overview of lipid peroxidation, as well as key components involved in the ferroptotic cascade. We will also highlight the role of the NRF2 signaling pathway in mediating lipid peroxidation and ferroptosis, focusing on established NRF2 target genes that mitigate these pathways, as well as the relevance of the NRF2-lipid peroxidation-ferroptosis axis in disease.

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  • All ApoE isoforms increased the expression of known NRF2 target genes including SLC7A11, AKR1C1, and FTH1.

    “and increased the expression of known target genes of this transcription factor including SLC7A11, AKR1C1, and FTH1 (fig. S5S) (41–45).”

    From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [45]

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Authors
Dodson, M., Castro-Portuguez, R., & Zhang, D. D.
Affiliations
University of Arizona (US)
Corresponding author
Zhang, Donna D.
ORCID
Venue
Redox Biology
Publisher
Elsevier BV
Published
2019-05
Volume
23
Pages
101107
ISSN
2213-2317 (ISSN-L)
DOI
10.1016/j.redox.2019.101107
PMC
PMC6859567
OpenAlex
W2909817598
Cited by
2,435
References
9
Citations by year
2026: 396 · 2025: 551 · 2024: 589 · 2023: 356 · 2022: 293 · 2021: 149 · 2020: 83 · 2019: 12 · 2012: 1
FWCI
11.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Redox Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Environmental Health Sciences (ES026845)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK109555, P30 ES006694, P42 ES004940)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
Nrf2, lipid peroxidation, ferroptosis, antioxidant response, redox homeostasis, oxidative stress, electrophilic stress, Nrf2 target genes, iron-dependent cell death, lipid hydroperoxides, neurodegenerative diseases, cardiovascular disease, cancer therapy
MeSH terms
Ferroptosis, Animals, Humans, Neoplasms, Oxidation-Reduction, Lipid Peroxidation, Signal Transduction, Cell Death, Reactive Oxygen Species, Lipid Metabolism, NF-E2-Related Factor 2

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