ENTRY ko04216 Pathway NAME Ferroptosis DESCRIPTION Ferroptosis is a regulated form of cell death and characterized by a production of reactive oxygen species (ROS) from accumulated iron and lipid peroxidation. It can be induced by experimental compounds (e.g.,erastin, RSL3) or clinical drugs(e.g., sulfasalazine, sorafenib) in cancer cell and certain normal cells. It is involved in multiple physiological and pathological processes, such as cancer cell death, neurodegenerative disease, tissue damage and acute renal failure. CLASS Cellular Processes; Cell growth and death PATHWAY_MAP ko04216 Ferroptosis DBLINKS GO: 0097707 ORTHOLOGY K00460 ALOX15; arachidonate 15-lipoxygenase [EC:1.13.11.33] K00510 HMOX1; heme oxygenase 1 [EC:1.14.14.18] K00522 FTH1; ferritin heavy chain [EC:1.16.3.1] K00657 speG, SAT; diamine N-acetyltransferase [EC:2.3.1.57] K01897 ACSL, fadD; long-chain-fatty-acid---CoA ligase [EC:6.2.1.3] K04451 TP53, P53; tumor protein p53 K05361 GPX4; phospholipid-hydroperoxide glutathione peroxidase [EC:1.11.1.12] K05634 PRNP, PrP, CD230; prion protein K06503 TFRC, CD71; transferrin receptor K06519 SLC3A2, MDU1, CD98; solute carrier family 3, member 2 K08337 ATG7; ubiquitin-like modifier-activating enzyme ATG7 K08339 ATG5; autophagy-related protein 5 K09289 NCOA4, PTC3; nuclear receptor coactivator 4 K10142 STEAP3, TSAP6; metalloreductase STEAP3 [EC:1.16.1.-] K10435 MAP1LC; microtubule-associated protein 1 light chain K11204 GCLC; glutamate--cysteine ligase catalytic subunit [EC:6.3.2.2] K11205 GCLM; glutamate--cysteine ligase regulatory subunit K12889 PCBP1; poly(rC)-binding protein 1 K13162 PCBP2; poly(rC)-binding protein 2 K13515 LPCAT3, MBOAT5; lysophospholipid acyltransferase 5 [EC:2.3.1.23 2.3.1.-] K13624 CP; ceruloplasmin [EC:1.16.3.1] K13625 FTL; ferritin light chain K13869 SLC7A11; solute carrier family 7 (L-type amino acid transporter), member 11 K14685 SLC40A1, FPN1; solute carrier family 40 (iron-regulated transporter), member 1 K14714 SLC39A8, ZIP8; solute carrier family 39 (zinc transporter), member 8 K14720 SLC39A14, ZIP14; solute carrier family 39 (zinc transporter), member 14 K14736 TF; transferrin K15040 VDAC2; voltage-dependent anion channel protein 2 K15041 VDAC3; voltage-dependent anion channel protein 3 K18495 FTMT; ferritin, mitochondrial [EC:1.16.3.1] K21398 SLC11A2, DMT1, NRAMP2; natural resistance-associated macrophage protein 2 K21421 NOX2, GP91, CYBB; NADPH oxidase 2 [EC:1.-.-.-] K21456 GSS; glutathione synthase [EC:6.3.2.3] COMPOUND C00010 CoA C00024 Acetyl-CoA C00025 L-Glutamate C00027 Hydrogen peroxide C00032 Heme C00051 Glutathione C00097 L-Cysteine C00127 Glutathione disulfide C00129 Isopentenyl diphosphate C00219 Arachidonate C00356 (S)-3-Hydroxy-3-methylglutaryl-CoA C00418 (R)-Mevalonate C00491 L-Cystine C00669 gamma-L-Glutamyl-L-cysteine C02249 Arachidonyl-CoA C02477 alpha-Tocopherol C11378 Ubiquinone-10 C14818 Fe2+ C14819 Fe3+ C16170 (7Z,10Z,13Z,16Z)-Docosatetraenoyl-CoA C16527 Adrenic acid C16844 Hydroxyl radical C21478 Erastin C21479 RSL3 C21480 1-Octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine C21481 1-Octadecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-sn-glycero-3-phosphoethanolamine C21482 1-Octadecanoyl-2-(15S-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine C21483 1-Octadecanoyl-2-(15S-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine C21484 1-Octadecanoyl-sn-glycero-3-phosphoethanolamine D00448 Sulfasalazine (USP/INN) D08524 Sorafenib (USAN/INN) REFERENCE PMID:26775689 AUTHORS Conrad M, Angeli JP, Vandenabeele P, Stockwell BR TITLE Regulated necrosis: disease relevance and therapeutic opportunities. JOURNAL Nat Rev Drug Discov 15:348-66 (2016) DOI:10.1038/nrd.2015.6 REFERENCE PMID:26653790 AUTHORS Yang WS, Stockwell BR TITLE Ferroptosis: Death by Lipid Peroxidation. JOURNAL Trends Cell Biol 26:165-76 (2016) DOI:10.1016/j.tcb.2015.10.014 REFERENCE PMID:27842066 AUTHORS Kagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS, Dar HH, Liu B, Tyurin VA, Ritov VB, Kapralov AA, Amoscato AA, Jiang J, Anthonymuthu T, Mohammadyani D, Yang Q, Proneth B, Klein-Seetharaman J, Watkins S, Bahar I, Greenberger J, Mallampalli RK, Stockwell BR, Tyurina YY, Conrad M, Bayir H TITLE Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. JOURNAL Nat Chem Biol 13:81-90 (2017) DOI:10.1038/nchembio.2238 REFERENCE PMID:27842067 AUTHORS D'Herde K, Krysko DV TITLE Ferroptosis: Oxidized PEs trigger death. JOURNAL Nat Chem Biol 13:4-5 (2017) DOI:10.1038/nchembio.2261 REFERENCE PMID:28082232 AUTHORS Guiney SJ, Adlard PA, Bush AI, Finkelstein DI, Ayton S TITLE Ferroptosis and cell death mechanisms in Parkinson's disease. JOURNAL Neurochem Int 104:34-48 (2017) DOI:10.1016/j.neuint.2017.01.004 REFERENCE PMID:26725301 AUTHORS Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y TITLE Regulators of Iron Homeostasis: New Players in Metabolism, Cell Death, and Disease. JOURNAL Trends Biochem Sci 41:274-86 (2016) DOI:10.1016/j.tibs.2015.11.012 REFERENCE PMID:26794443 AUTHORS Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, Kang R, Tang D TITLE Ferroptosis: process and function. JOURNAL Cell Death Differ 23:369-79 (2016) DOI:10.1038/cdd.2015.158 REFERENCE PMID:27791175 AUTHORS Murphy ME TITLE Ironing out how p53 regulates ferroptosis. JOURNAL Proc Natl Acad Sci U S A 113:12350-12352 (2016) DOI:10.1073/pnas.1615159113 REFERENCE PMID:28129536 AUTHORS Muckenthaler MU, Rivella S, Hentze MW, Galy B TITLE A Red Carpet for Iron Metabolism. JOURNAL Cell 168:344-361 (2017) DOI:10.1016/j.cell.2016.12.034 REFERENCE PMID:27860262 AUTHORS Yu H, Guo P, Xie X, Wang Y, Chen G TITLE Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. JOURNAL J Cell Mol Med 21:648-657 (2017) DOI:10.1111/jcmm.13008 REFERENCE PMID:27314071 AUTHORS Wang SJ, Ou Y, Jiang L, Gu W TITLE Ferroptosis: A missing puzzle piece in the p53 blueprint? JOURNAL Mol Cell Oncol 3:e1046581 (2016) DOI:10.1080/23723556.2015.1046581 REFERENCE PMID:27048822 AUTHORS Cao JY, Dixon SJ TITLE Mechanisms of ferroptosis. JOURNAL Cell Mol Life Sci 73:2195-209 (2016) DOI:10.1007/s00018-016-2194-1 REFERENCE PMID:26436293 AUTHORS Mancias JD, Pontano Vaites L, Nissim S, Biancur DE, Kim AJ, Wang X, Liu Y, Goessling W, Kimmelman AC, Harper JW TITLE Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. JOURNAL Elife 4:e10308 (2015) DOI:10.7554/eLife.10308 REFERENCE PMID:28066232 AUTHORS Wang YQ, Chang SY, Wu Q, Gou YJ, Jia L, Cui YM, Yu P, Shi ZH, Wu WS, Gao G, Chang YZ TITLE The Protective Role of Mitochondrial Ferritin on Erastin-Induced Ferroptosis. JOURNAL Front Aging Neurosci 8:308 (2016) DOI:10.3389/fnagi.2016.00308 REFERENCE PMID:26405158 AUTHORS Kwon MY, Park E, Lee SJ, Chung SW TITLE Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death. JOURNAL Oncotarget 6:24393-403 (2015) DOI:10.18632/oncotarget.5162 REFERENCE PMID:22632964 AUTHORS Reed JC, Pellecchia M TITLE Ironing out cell death mechanisms. JOURNAL Cell 149:963-5 (2012) DOI:10.1016/j.cell.2012.05.009 REL_PATHWAY ko00480 Glutathione metabolism ko00900 Terpenoid backbone biosynthesis ///