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Review
. 2017 Oct 5;171(2):273-285.
doi: 10.1016/j.cell.2017.09.021.

Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

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Review

Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

Brent R Stockwell et al. Cell. .

Abstract

Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.

Keywords: PUFA; ROS; cancer; cell death; ferroptosis; glutathione; iron; metabolism; neurodegeneration; peroxidation.

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Figures

Figure 1
Figure 1. GPX4 uses glutathione to eliminate lipid peroxides formed in phospholipids containing polyunsaturated fatty acids
System xc- imports cystine, which is reduced to cysteine and used to synthesize glutathione, a necessary cofactor of GPX4 for eliminating lipid peroxides.
Figure 2
Figure 2. Pathways controlling ferroptosis
The indicated pathways regulate ferroptosis sensitivity.

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