SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis
Copyright © 2023. Published by Elsevier B.V..
Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not clear yet. Here, we find SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. SARS-CoV-2 ORF3a promotes the degradation of NRF2 through recruiting Keap1, thereby attenuating cellular resistance to oxidative stress and facilitated cells to ferroptotic cell death. Our study uncovers that SARS-CoV-2 ORF3a functions as a positive regulator of ferroptosis, which might explain SARS-CoV-2-induced damage in multiple organs in COVID-19 patients and imply the potential of ferroptosis inhibition in COVID-19 treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
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| Enthalten in: |
Redox biology - 63(2023) vom: 15. Juli, Seite 102752 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Lihong [VerfasserIn] |
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| Links: |
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| Themen: |
Ferroptosis |
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| Anmerkungen: |
Date Completed 07.06.2023 Date Revised 15.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.redox.2023.102752 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM357475054 |
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| 520 | |a Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not clear yet. Here, we find SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. SARS-CoV-2 ORF3a promotes the degradation of NRF2 through recruiting Keap1, thereby attenuating cellular resistance to oxidative stress and facilitated cells to ferroptotic cell death. Our study uncovers that SARS-CoV-2 ORF3a functions as a positive regulator of ferroptosis, which might explain SARS-CoV-2-induced damage in multiple organs in COVID-19 patients and imply the potential of ferroptosis inhibition in COVID-19 treatment | ||
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| 700 | 1 | |a Yang, Sidi |e verfasserin |4 aut | |
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| 700 | 1 | |a Shen, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jiacheng |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Liu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Siyao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xue |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Liping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chunmei |e verfasserin |4 aut | |
| 700 | 1 | |a Ke, Changwen |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Xiaofang |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Deyin |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Hong |e verfasserin |4 aut | |
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