| Autor: |
Tamil S. Anthonymuthu, Yulia Y. Tyurina, Wan-Yang Sun, Karolina Mikulska-Ruminska, Indira H. Shrivastava, Vladimir A. Tyurin, Fatma B. Cinemre, Haider H. Dar, Andrew P. VanDemark, Theodore R. Holman, Yoel Sadovsky, Brent R. Stockwell, Rong-Rong He, Ivet Bahar, Hülya Bayır, Valerian E. Kagan |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 38, Iss , Pp 101744- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2020.101744 |
| Popis: |
Hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) is a ferroptotic cell death signal. HpETE-PE is produced by the 15-Lipoxygenase (15LOX)/Phosphatidylethanolamine Binding Protein-1 (PEBP1) complex or via an Fe-catalyzed non-enzymatic radical reaction. Ferrostatin-1 (Fer-1), a common ferroptosis inhibitor, is a lipophilic radical scavenger but a poor 15LOX inhibitor arguing against 15LOX having a role in ferroptosis. In the current work, we demonstrate that Fer-1 does not affect 15LOX alone, however, it effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows that Fer-1 binds to the 15LOX/PEBP1 complex at three sites and could disrupt the catalytically required allosteric motions of the 15LOX/PEBP1 complex. Using nine ferroptosis cell/tissue models, we show that HpETE-PE is produced by the 15LOX/PEBP1 complex and resolve the long-existing Fer-1 anti-ferroptotic paradox. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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