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. 2022 Nov 4;13:977062. doi: 10.3389/fphar.2022.977062

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Copyright © 2022 Dai, Li, Long, Zhou, Luo, Xu and Gao.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The regulatory mechanism of ferroptosis. The regulatory network of ferroptosis is mainly divided into two categories: Oxidation system and antioxidant system. The oxidation system includes iron metabolism, lipid metabolism, glutamate metabolism, etc. The antioxidant system includes system xc⁻/GSH/GPX4 axis, FSP1/CoQ10/NAD (P) H axis, GCH1/BH4 axis, etc. Iron metabolism: Transferrin (TF); Transferrin receptor 1 (TFRC); Six transmembrane epithelial antigen of protein 3 (STEAP3); Divalent metal ion transporter 1 (DMT1); Zinc transporter 8/14 (ZIP8/14); Labile iron pool (LIP); ferroportin (FPN); Ferritin heavy chain 1 (FTH1); Ferritin light chain (FTL); Solute carrier family member 11A2 (SLC11A2); Iron response element binding protein 2 (IREB2); Reactive oxygen species (ROS); Poly (RC) binding protein 2 (PCBP2); Nuclear receptor coactivator 4 (NCOA4); Multivesicular bodies (MVB). Lipid metabolism: Polyunsaturated fatty acid (PUFA); Long chain acyl CoA synthetase 4 (ACSL4); Lysophosphatidylcholine acyltransferase 3 (LPCAT3); Phosphatidylethanolamine (PE); Arachidonic acid lipid peroxidase (ALOX). Glutamate metabolism: Glutamine transporter (SLC1A5); Glutamic acid cysteine ligase 1 (GCL1); Glutamic acid cysteine ligase 2 (GCL2); Glutamic-oxaloacetic transaminase 1 (GOT1); α- Ketoglutarate (α KG). Tricarboxylic acid cycle (TCA cycle). System xc^-/GSH/GPX4 axis: Cystine/glutamate antiporter (system xc⁻); Solute carrier family member 7A11 (SLC7A11); Solute carrier family member 3A2 (SLC3A2); Glutathione (GSH); Thioredoxin reductase 1 (TXNRD1); Glutamic acid cysteine ligase (GCL); Glutathione synthetase (GSS); Glutathione peroxidase 4 (GPX4); oxidized glutathione (GSSG); Selenium (Se). FSP1/CoQ10/NAD (P) H axis: ferroptosis suppressor protein 1 (FSP1); Oxidized coenzyme Q10 (CoQ10); Reduced coenzyme Q10 (CoQ10H₂). 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA); 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR); Mevalonate (MVA); Isopentenyl pyrophosphate (IPP); Farnesyl pyrophosphate (FPP); Geranylgeranyl pyrophosphate (GGPP). GCH1/BH4 axis: Guanosine triphosphate (GTP); GTP cyclohydrolase 1 (GCH1); Tetrahydrobiopterin (BH4); Other regulatory factors: Nuclear factor E2 related factor 2 (NRF2); Heme oxygenase 1 (HO-1); NAD (P) H-dependent quinone oxidoreductase 1 (NQO1); Kelch like ECH associated protein 1 (KEAP1); Cullin3 (CUL3); Activating transcription factor 4 (ATF4); Activating transcription factor 4 (ATF4); OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1); Beclin1(BECN1); AMP activated protein kinase (AMPK); BRCA1 related protein 1 (BAP1); Histone 2A ubiquitination (H2AUB); Yes associated protein 1 (YAP1); Signal transducer and activator of transcription 3 (STAT3).