Ferroptosis: machinery and regulation

By Xin Chen, Jingbo Li, R. Kang, D. Klionsky, D. Tang. Autophagy, 2020

1,799 citations recorded by the source corpus.

ABSTRACT Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which is controlled by integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase is the main promoter of ferroptosis by producing lipid hydroperoxides, and its function relies on the activation of ACSL4-dependent lipid biosynthesis. In contrast, the selenium-containing enzyme GPX4 is currently recognized as a central repressor of ferroptosis, and its activity depends on glutathione produced from the activation of the cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, and amino acids) and degradation pathways (macroautophagy/autophagy and the ubiquitin-proteasome system) orchestrate the complex ferroptotic response through direct or indirect regulation of iron accumulation or lipid peroxidation. Although the detailed mechanism of membrane injury during ferroptosis remains a mystery, ESCRT III-mediated plasma membrane repair can make cells resistant to ferroptosis. Here, we review the recent rapid progress in understanding the molecular mechanisms of ferroptosis and focus on the epigenetic, transcriptional, and posttranslational regulation of this process. Abbreviations: 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear cell renal cell carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated fatty acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated fatty acid; RCD: regulated cell death; RNS: reactive nitrogen species; ROS: reactive oxygen species; RTAs: radical-trapping antioxidants; UPS: ubiquitin-proteasome system; UTR: untranslated region.

Subfields: Cancer Research, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/115bb6b5e1d440b24cb591120e82a1646c6a3f43

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. D. Tang
2. Guido Kroemer
3. R. Kang
4. Xin Chen

In Molecular Biology

1. Guido Kroemer
2. D. Tang
3. R. Kang
4. Xin Chen
5. D. Klionsky
6. Beth Levine
7. L. Galluzzi
8. N. Mizushima

In Pulmonary and Respiratory Medicine

1. D. Tang
2. Guido Kroemer
3. R. Kang
4. Xin Chen
5. D. Klionsky
6. Jinbao Liu
7. Brent R. Stockwell
8. Jiao Liu

Citations in the corpus

• Ferroptosis: molecular mechanisms and health implications (2020, background): “In general, ferroptosis is considered to be a form of regulated necrosis, which is strictly controlled at multiple levels.(202,203) Ferroptosis can occur by targeting two main pathways, the extrinsic or transporter (e.”
• Copper metabolism in cell death and autophagy (2023, background): “Ferroptosis can be caused by both intrinsic and extrinsic pathways [129,130].”
• Ferroptosis in infection, inflammation, and immunity (2021, background): “Signaling and process of ferroptosis In the past 5 yr, combining genetic technology and pharmacological approaches, our understanding of the molecular machinery of ferroptosis has rapidly improved and been fine-tuned at the epigenetic, transcriptional, and posttranslational levels (Chen et al., 2020”