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A guide to ferroptosis, the biological rust of cellular membranes

Journal

FEBS JOURNAL
Volume -, Issue -, Pages -

Publisher

WILEY
DOI: 10.1111/febs.16993

Keywords

ferroptosis; FSP1; GPX4; iron; lipid; lipid peroxidation; metabolism; radical trapping antioxidant; redox

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Ferroptosis is a cell death mechanism that occurs through excessive peroxidation of polyunsaturated fatty acids within cellular membranes, catalyzed by iron. This process is tightly regulated by lipid, iron, and redox metabolic processes. This review provides an overview of how ferroptosis is executed, including the major classes of inducers and inhibitors, as well as methods for detection. The detrimental role of ferroptosis in disease is also briefly discussed.
Unprotected iron can rust due to oxygen exposure. Similarly, in our body, oxidative stress can kill cells in an iron-dependent manner, which can give rise to devastating diseases. This type of cell death is referred to as ferroptosis. Generally, ferroptosis is defined as an iron-catalyzed form of regulated necrosis that occurs through excessive peroxidation of polyunsaturated fatty acids within cellular membranes. This review summarizes how ferroptosis is executed by a rather primitive biochemical process, under tight regulation of lipid, iron, and redox metabolic processes. An overview is given of major classes of ferroptosis inducers and inhibitors, and how to detect ferroptosis. Finally, its detrimental role in disease is briefly discussed. Ferroptosis is defined as an iron-catalyzed form of regulated necrosis that occurs through excessive peroxidation of polyunsaturated fatty acids within cellular membranes. The propagation of lipid radicals in this radical chain reaction ultimately results in the destruction of the cellular wall. The biochemical process of ferroptosis execution is tightly controlled by iron metabolism, antioxidant defense, and lipid metabolism.image

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