Academic Journal
Cysteine and homocysteine can be exploited by GPX4 in ferroptosis inhibition independent of GSH synthesis
| العنوان: | Cysteine and homocysteine can be exploited by GPX4 in ferroptosis inhibition independent of GSH synthesis |
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| المؤلفون: | Chaoyi Xia, Xiyue Xing, Wenxia Zhang, Yang Wang, Xin Jin, Meihong Tian, Xueqing Ba, Fengqi Hao |
| المصدر: | Redox Biology, Vol 69, Iss , Pp 102999- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
| مصطلحات موضوعية: | Cysteine, Homocysteine, GSH, Glutathione peroxidase 4, Ferroptosis, Medicine (General), R5-920, Biology (General), QH301-705.5 |
| الوصف: | Ferroptosis is inhibited by glutathione peroxidase 4 (GPX4), an antioxidant enzyme that uses reduced glutathione (GSH) as a cofactor to detoxify lipid hydroperoxides. As a selenoprotein, the core function of GPX4 is the thiol-dependent redox reaction. In addition to GSH, other small molecules such as cysteine and homocysteine also contain thiols; yet, whether GPX4 can exploit cysteine and homocysteine to directly detoxify lipid hydroperoxides and inhibit ferroptosis has not been addressed. In this study, we found that cysteine and homocysteine inhibit ferroptosis in a GPX4-dependent manner. However, cysteine inhibits ferroptosis independent of GSH synthesis, and homocysteine inhibits ferroptosis through non-cysteine and non-GSH pathway. Furthermore, we used molecular docking and GPX4 activity analysis to study the binding patterns and affinity between GPX4 and GSH, cysteine, and homocysteine. We found that besides GSH, cysteine and homocysteine are also able to serve as substrates for GPX4 though the affinities of GPX4 with cysteine and homocysteine are lower than that with GSH. Importantly, GPX family and the GSH synthetase pathway might be asynchronously evolved. When GSH synthetase is absent, for example in Flexibacter, the fGPX exhibits higher affinity with cysteine and homocysteine than GSH. Taken together, the present study provided the understanding of the role of thiol-dependent redox systems in protecting cells from ferroptosis and propose that GSH might be a substitute for cysteine or homocysteine to be used as a cofactor for GPX4 during the evolution of aerobic metabolism. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2213-2317 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2213231723004007; https://doaj.org/toc/2213-2317 |
| DOI: | 10.1016/j.redox.2023.102999 |
| URL الوصول: | https://doaj.org/article/a28c4d3d14c94e7a923469044bf306fc |
| رقم الانضمام: | edsdoj.28c4d3d14c94e7a923469044bf306fc |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22132317 |
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| DOI: | 10.1016/j.redox.2023.102999 |