KEGG   PATHWAY: ko04216
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
ko04216

Disease
H02206  Aceruloplasminemia
H02312  Glutathione synthetase deficiency
Other DBs
GO: 0097707
Orthology
K06519  solute carrier family 3, member 2
K13869  solute carrier family 7 (L-type amino acid transporter), member 11
K11204  glutamate--cysteine ligase catalytic subunit [EC:6.3.2.2]
K11205  glutamate--cysteine ligase regulatory subunit
K21456  glutathione synthase [EC:6.3.2.3]
K05361  phospholipid-hydroperoxide glutathione peroxidase [EC:1.11.1.12]
K00460  arachidonate 15-lipoxygenase [EC:1.13.11.33]
K13515  lysophospholipid acyltransferase 5 [EC:2.3.1.23 2.3.1.-]
K01897  long-chain acyl-CoA synthetase [EC:6.2.1.3]
K04451  tumor protein p53
K00657  diamine N-acetyltransferase [EC:2.3.1.57]
K14736  transferrin
K06503  transferrin receptor
K10142  metalloreductase STEAP3 [EC:1.16.1.-]
K21398  natural resistance-associated macrophage protein 2
K14714  solute carrier family 39 (zinc transporter), member 8
K14720  solute carrier family 39 (zinc transporter), member 14
K13162  poly(rC)-binding protein 2
K14685  solute carrier family 40 (iron-regulated transporter), member 1
K13624  ceruloplasmin [EC:1.16.3.1]
K12889  poly(rC)-binding protein 1
K00522  ferritin heavy chain [EC:1.16.3.2]
K13625  ferritin light chain
K10435  microtubule-associated protein 1 light chain
K08339  autophagy-related protein 5
K08337  ubiquitin-like modifier-activating enzyme ATG7
K09289  nuclear receptor coactivator 4
K05634  prion protein
K00510  heme oxygenase 1 [EC:1.14.14.18]
K15040  voltage-dependent anion channel protein 2
K15041  voltage-dependent anion channel protein 3
K21421  NADPH oxidase 2 [EC:1.-.-.-]
K18495  ferritin, mitochondrial
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
Related
pathway
ko00480  Glutathione metabolism
ko00900  Terpenoid backbone biosynthesis
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