NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis
By M. Dodson, Raul Castro-Portuguez, Donna D. Zhang. Redox Biology, 2019
2,087 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/e65c567bb4b6a1f5b460dff3b5f67c8a8af16dcf
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In Molecular Biology
In Pulmonary and Respiratory Medicine
Citations in the corpus
- Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis (2022, background): “Nrf2 is a key factor in determining the therapeutic response of ferroptosis-targeted therapies [54].”
- ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis (2023, background): “NRF2 is an important regulator not only of GPX4 expression but also of other important antioxidant defense system components, making it a multifaceted regulator of the antiferroptotic reaction (Dodson et al. 2019).”
- The interaction between ferroptosis and lipid metabolism in cancer (2020, background): “Furthermore, many other proteins and enzymes, such as GPX4, NADPH, FTH1, FTL, and ferroportin, which are responsible for preventing lipid peroxidation and thus cause ferroptosis, are the target genes of Nrf2.”