tetano
Editor, Senior Moderator
Redox Biol
. 2023 May 23;63:102752.
doi: 10.1016/j.redox.2023.102752. Online ahead of print. SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis
Lihong Liu[SUP] 1 [/SUP], Jie Du[SUP] 2 [/SUP], Sidi Yang[SUP] 3 [/SUP], Birong Zheng[SUP] 1 [/SUP], Jian Shen[SUP] 4 [/SUP], Jiacheng Huang[SUP] 3 [/SUP], Liu Cao[SUP] 2 [/SUP], Siyao Huang[SUP] 2 [/SUP], Xue Liu[SUP] 2 [/SUP], Liping Guo[SUP] 5 [/SUP], Chunmei Li[SUP] 2 [/SUP], Changwen Ke[SUP] 6 [/SUP], Xiaofang Peng[SUP] 6 [/SUP], Deyin Guo[SUP] 7 [/SUP], Hong Peng[SUP] 8 [/SUP]
Affiliations
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.
Keywords: Ferroptosis; Keap1; NRF2; ORF3a; SARS-CoV-2.
. 2023 May 23;63:102752.
doi: 10.1016/j.redox.2023.102752. Online ahead of print. SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis
Lihong Liu[SUP] 1 [/SUP], Jie Du[SUP] 2 [/SUP], Sidi Yang[SUP] 3 [/SUP], Birong Zheng[SUP] 1 [/SUP], Jian Shen[SUP] 4 [/SUP], Jiacheng Huang[SUP] 3 [/SUP], Liu Cao[SUP] 2 [/SUP], Siyao Huang[SUP] 2 [/SUP], Xue Liu[SUP] 2 [/SUP], Liping Guo[SUP] 5 [/SUP], Chunmei Li[SUP] 2 [/SUP], Changwen Ke[SUP] 6 [/SUP], Xiaofang Peng[SUP] 6 [/SUP], Deyin Guo[SUP] 7 [/SUP], Hong Peng[SUP] 8 [/SUP]
Affiliations
- PMID: 37245288
- DOI: 10.1016/j.redox.2023.102752
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.
Keywords: Ferroptosis; Keap1; NRF2; ORF3a; SARS-CoV-2.