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Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response
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 resp...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Molecular and Cellular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070163/ https://www.ncbi.nlm.nih.gov/pubmed/36994475 http://dx.doi.org/10.14348/molcells.2023.0005 |
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author | Shakya, Aryatara McKee, Nicholas W. Dodson, Matthew Chapman, Eli Zhang, Donna D. |
author_facet | Shakya, Aryatara McKee, Nicholas W. Dodson, Matthew Chapman, Eli Zhang, Donna D. |
author_sort | Shakya, Aryatara |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10070163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-100701632023-04-05 Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response Shakya, Aryatara McKee, Nicholas W. Dodson, Matthew Chapman, Eli Zhang, Donna D. Mol Cells Minireview 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. Korean Society for Molecular and Cellular Biology 2023-03-31 2023-03-24 /pmc/articles/PMC10070163/ /pubmed/36994475 http://dx.doi.org/10.14348/molcells.2023.0005 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/) |
spellingShingle | Minireview Shakya, Aryatara McKee, Nicholas W. Dodson, Matthew Chapman, Eli Zhang, Donna D. Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response |
title | Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response |
title_full | Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response |
title_fullStr | Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response |
title_full_unstemmed | Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response |
title_short | Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response |
title_sort | anti-ferroptotic effects of nrf2: beyond the antioxidant response |
topic | Minireview |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070163/ https://www.ncbi.nlm.nih.gov/pubmed/36994475 http://dx.doi.org/10.14348/molcells.2023.0005 |
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