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Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation. [PDF]
Adv Sci (Weinh)Cui S, Ye J.
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Small-molecule allosteric inhibitors of GPX4
Cell Chemical Biology, 2022Encouraged by the dependence of drug-resistant, metastatic cancers on GPX4, we examined biophysical mechanisms of GPX4 inhibition, which revealed an unexpected allosteric site. We found that this site was involved in native regeneration of GPX4 under low glutathione conditions.
Hengrui Liu +2 more
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GPX4: old lessons, new features
Biochemical Society Transactions, 2022GPX4 is a selenocysteine-containing protein that plays an essential role in repairing peroxidised phospholipids. Its role in organismal homeostasis has been known for decades, and it has been reported to play a pivotal role in cell survival and mammalian embryonic development.
Thamara, Nishida Xavier da Silva +2 more
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Structure–activity relationships of GPX4 inhibitor warheads
Bioorganic and Medicinal Chemistry Letters, 2020 Direct inhibition of GPX4 requires covalent modification of the active-site selenocysteine. While phenotypic screening has revealed that activated alkyl chlorides and masked nitrile oxides can inhibit GPX4 covalently, a systematic assessment of potential electrophilic warheads with the capacity to inhibit cellular GPX4 has been lacking. Here, we survey
John K Eaton +2 more
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Copper-dependent autophagic degradation of GPX4 drives ferroptosis
Autophagy, 2023 Ferroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays a master role in blocking ferroptosis by eliminating phospholipid hydroperoxides, the regulation of GPX4 remains poorly understood.
Rui Kang +2 more
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GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis
Proteomics, 2019Abstract Oxygen is necessary for aerobic metabolism but can cause the harmful oxidation of lipids and other macromolecules. Oxidation of cholesterol and phospholipids containing polyunsaturated fatty acyl chains can lead to lipid peroxidation, membrane damage, and cell death.
Giovanni C Forcina, Scott J Dixon
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GPX4, ferroptosis, and diseases
Biomedicine and PharmacotherapyGPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing a significant role in maintaining the redox homeostasis within the body. Ferroptosis, a form of iron-dependent non-apoptotic cell death, has gained considerable attention in recent years due to its ...
Wangzheqi, Zhang +4 more
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Pathophysiology, 2017 Oxidative stress is implicated in the pathologies of vascular endothelial cells. However, the importance of specific antioxidant enzymes in vascular endothelial cells is not fully understood. The purpose of this study was to elucidate the importance of Glutathione peroxidase 4 (GPx4), and the involvement of ferroptosis on cell death induced by GPx4 ...
Takashi Ueta +2 more
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2019
Glutathione peroxidase 4 (Gpx4) is a monomeric glutathione peroxidase with a unique ability to reduce hydroperoxide in complex lipids. Gpx4 is vital for development, and its function is also indispensable for many cell types of adult animal. Ferroptosis is an iron-dependent oxidative cell death. In ferroptosis, a high load of hydroperoxides in membrane
Qitao Ran, Paulina Mozolewska
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Glutathione peroxidase 4 (Gpx4) is a monomeric glutathione peroxidase with a unique ability to reduce hydroperoxide in complex lipids. Gpx4 is vital for development, and its function is also indispensable for many cell types of adult animal. Ferroptosis is an iron-dependent oxidative cell death. In ferroptosis, a high load of hydroperoxides in membrane
Qitao Ran, Paulina Mozolewska
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GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2023Glutathione peroxidase 4 (GPx4) moonlights as structural protein and antioxidase that powerfully inhibits lipid oxidation. In the past years, it is considered as a key regulator of ferroptosis, which takes role in the lipid and amine acid metabolism and influences the cell aging, oncogenesis, and cell death.
Yi, Liu +4 more
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