Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis
Ferroptosis induced by erastin (an inhibitor of cystine transport) and butionine sulfoximine (an inhibitor of glutathione biosynthesis) was prevented by the mitochondria-targeted antioxidants SkQ1 and MitoTEMPO. These effects correlate with the prevention of mitochondrial lipid peroxidation, which p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/4/611 |
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| author | Konstantin G. Lyamzaev Alisa A. Panteleeva Ruben A. Simonyan Armine V. Avetisyan Boris V. Chernyak |
| author_facet | Konstantin G. Lyamzaev Alisa A. Panteleeva Ruben A. Simonyan Armine V. Avetisyan Boris V. Chernyak |
| author_sort | Konstantin G. Lyamzaev |
| collection | DOAJ |
| description | Ferroptosis induced by erastin (an inhibitor of cystine transport) and butionine sulfoximine (an inhibitor of glutathione biosynthesis) was prevented by the mitochondria-targeted antioxidants SkQ1 and MitoTEMPO. These effects correlate with the prevention of mitochondrial lipid peroxidation, which precedes cell death. Methylene blue, a redox agent that inhibits the production of reactive oxygen species (ROS) in complex I of the mitochondrial electron transport chain, also inhibits ferroptosis and mitochondrial lipid peroxidation. Activation of ROS production in complex I with rotenone in the presence of ferrous iron stimulates lipid peroxidation in isolated mitochondria, while ROS produced by complex III are ineffective. SkQ1 and methylene blue inhibit lipid peroxidation. We suggest that ROS formed in complex I promote mitochondrial lipid peroxidation and ferroptosis. |
| first_indexed | 2024-03-11T09:00:58Z |
| format | Article |
| id | doaj.art-82e0faa0c5e44d039164f4c64776998d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:00:58Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-82e0faa0c5e44d039164f4c64776998d2023-11-16T19:44:46ZengMDPI AGCells2073-44092023-02-0112461110.3390/cells12040611Mitochondrial Lipid Peroxidation Is Responsible for FerroptosisKonstantin G. Lyamzaev0Alisa A. Panteleeva1Ruben A. Simonyan2Armine V. Avetisyan3Boris V. Chernyak4Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaFerroptosis induced by erastin (an inhibitor of cystine transport) and butionine sulfoximine (an inhibitor of glutathione biosynthesis) was prevented by the mitochondria-targeted antioxidants SkQ1 and MitoTEMPO. These effects correlate with the prevention of mitochondrial lipid peroxidation, which precedes cell death. Methylene blue, a redox agent that inhibits the production of reactive oxygen species (ROS) in complex I of the mitochondrial electron transport chain, also inhibits ferroptosis and mitochondrial lipid peroxidation. Activation of ROS production in complex I with rotenone in the presence of ferrous iron stimulates lipid peroxidation in isolated mitochondria, while ROS produced by complex III are ineffective. SkQ1 and methylene blue inhibit lipid peroxidation. We suggest that ROS formed in complex I promote mitochondrial lipid peroxidation and ferroptosis.https://www.mdpi.com/2073-4409/12/4/611ferroptosismitochondriacomplex ImtROSmitochondria targeted antioxidants |
| spellingShingle | Konstantin G. Lyamzaev Alisa A. Panteleeva Ruben A. Simonyan Armine V. Avetisyan Boris V. Chernyak Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis Cells ferroptosis mitochondria complex I mtROS mitochondria targeted antioxidants |
| title | Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis |
| title_full | Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis |
| title_fullStr | Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis |
| title_full_unstemmed | Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis |
| title_short | Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis |
| title_sort | mitochondrial lipid peroxidation is responsible for ferroptosis |
| topic | ferroptosis mitochondria complex I mtROS mitochondria targeted antioxidants |
| url | https://www.mdpi.com/2073-4409/12/4/611 |
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