GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis

By G. Forcina, Scott J. Dixon. Proteomics, 2019

927 citations recorded by the source corpus.

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. Lipid hydroperoxides are key intermediates in the process of lipid peroxidation. The lipid hydroperoxidase glutathione peroxidase 4 (GPX4) converts lipid hydroperoxides to lipid alcohols, and this process prevents the iron (Fe2+)‐dependent formation of toxic lipid reactive oxygen species (ROS). Inhibition of GPX4 function leads to lipid peroxidation and can result in the induction of ferroptosis, an iron‐dependent, non‐apoptotic form of cell death. This review describes the formation of reactive lipid species, the function of GPX4 in preventing oxidative lipid damage, and the link between GPX4 dysfunction, lipid oxidation, and the induction of ferroptosis.

Subfields: Oncology, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/127d68538cad0d201dbc47b6a21ab044a417a512

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In Pulmonary and Respiratory Medicine

1. P. Lei
2. Furong Zeng
3. Yu Meng
4. Yihuang Liu
5. Guangtong Deng
6. Xiang Chen
7. Yuming Sun
8. Jiayuan Le

Citations in the corpus

• Ferroptosis: mechanisms and links with diseases (2021, background): “GPx4 regulation—GSH axis: GSH is essential for the GPx4catalyzed reaction as it serves as an electron donor for reducing toxic phospholipid hydroperoxides (such as PE-AA-OOH/PE-AdAOOH) to nontoxic phospholipid alcohols (such as PE-AA-OH, PEAdA-OH), and the GSSG is generated as a by-product.(87) GSH ”
• Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies (2024, background): “122,123 By examining the crystal structure of seleno-GPX4, researchers observed the existence of seleninic acid (GPX4-Se-OO-) within the enzyme ’ s active site.”