KEGG   PATHWAY: rkg04216
Entry
rkg04216                    Pathway                                
Name
Ferroptosis - Rhinichthys klamathensis goyatoka (western speckled dace)
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
rkg04216  Ferroptosis
rkg04216

Other DBs
GO: 0097707
Organism
Rhinichthys klamathensis goyatoka (western speckled dace) [GN:rkg]
Gene
130073992  slc3a2b; solute carrier family 3 member 2b [KO:K06519]
130103377  4F2 cell-surface antigen heavy chain-like [KO:K06519]
130103379  zgc:158423; 4F2 cell-surface antigen heavy chain [KO:K06519]
130103947  slc7a11; cystine/glutamate transporter [KO:K13869]
130069539  si:ch73-352p4.8; cystine/glutamate transporter [KO:K13869]
130076855  cellular tumor antigen p53-like [KO:K04451]
130071217  tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
130092321  gclc; glutamate--cysteine ligase catalytic subunit [KO:K11204] [EC:6.3.2.2]
130091628  gclm; glutamate--cysteine ligase regulatory subunit [KO:K11205]
130070789  gss; glutathione synthetase [KO:K21456] [EC:6.3.2.3]
130075349  gpx4b; phospholipid hydroperoxide glutathione peroxidase [KO:K05361] [EC:1.11.1.12]
130089248  gpx4a; glutathione peroxidase 4a isoform X1 [KO:K05361] [EC:1.11.1.12]
130073160  acsl3a; long-chain-fatty-acid--CoA ligase 3a [KO:K01897] [EC:6.2.1.3]
130102767  acsl5; long-chain-fatty-acid--CoA ligase 5 [KO:K01897] [EC:6.2.1.3]
130075590  acsl4a; long-chain-fatty-acid--CoA ligase 4 [KO:K01897] [EC:6.2.1.3]
130091879  acsl4b; long-chain-fatty-acid--CoA ligase 4b [KO:K01897] [EC:6.2.1.3]
130087258  acsl3b; long-chain-fatty-acid--CoA ligase 3b [KO:K01897] [EC:6.2.1.3]
130079529  acsl6; long-chain-fatty-acid--CoA ligase 6 isoform X1 [KO:K01897] [EC:6.2.1.3]
130072074  acsl1b; long-chain-fatty-acid--CoA ligase 1b [KO:K01897] [EC:6.2.1.3]
130082085  acsl2; long-chain-fatty-acid--CoA ligase 6 [KO:K01897] [EC:6.2.1.3]
130089479  acsl1a; long-chain-fatty-acid--CoA ligase 1a isoform X1 [KO:K01897] [EC:6.2.1.3]
130103633  lpcat3; lysophospholipid acyltransferase 5 [KO:K13515] [EC:2.3.1.23 2.3.1.-]
130083897  sat1b; diamine acetyltransferase 1b isoform X1 [KO:K00657] [EC:2.3.1.57]
130103388  sat2a.1; thialysine N-epsilon-acetyltransferase [KO:K00657] [EC:2.3.1.57]
130077579  thialysine N-epsilon-acetyltransferase-like [KO:K00657] [EC:2.3.1.57]
130078702  diamine acetyltransferase 1-like [KO:K00657] [EC:2.3.1.57]
130078705  sat1a.1; diamine acetyltransferase 1a.1 [KO:K00657] [EC:2.3.1.57]
130071117  sat2b; diamine acetyltransferase 2b [KO:K00657] [EC:2.3.1.57]
130083984  tfr1b; transferrin receptor 1b [KO:K06503]
130097979  tfr1a; transferrin receptor 1a [KO:K06503]
130077775  slc11a2; natural resistance-associated macrophage protein 2 [KO:K21398]
130102894  slc39a8; metal cation symporter ZIP8 [KO:K14714]
130095642  metal cation symporter ZIP8 isoform X1 [KO:K14714]
130097175  slc39a14; metal cation symporter ZIP14 isoform X1 [KO:K14720]
130083622  pcbp2; poly(rC)-binding protein 2 isoform X1 [KO:K13162]
130072561  slc40a1; solute carrier family 40 member 1 [KO:K14685]
130070160  si:ch211-254p10.2; solute carrier family 40 member 1 [KO:K14685]
130075389  cp; ceruloplasmin [KO:K13624] [EC:1.16.3.1]
130084420  zgc:56095; ferritin, lower subunit-like [KO:K00522] [EC:1.16.3.1]
130091316  fth1a; ferritin, heavy polypeptide 1a [KO:K00522] [EC:1.16.3.1]
130106255  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
130106260  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
130106261  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
130106262  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
130106480  fth1b; ferritin, heavy polypeptide 1b [KO:K00522] [EC:1.16.3.1]
130089726  map1lc3cl; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
130085192  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
130085587  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
130084697  ncoa4; nuclear receptor coactivator 4 isoform X1 [KO:K09289]
130069794  hmox1a; heme oxygenase 1a isoform X1 [KO:K00510] [EC:1.14.14.18]
130083111  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
130078463  voltage-dependent anion-selective channel protein 2-like [KO:K15040]
130085553  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
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
Related
pathway
rkg00480  Glutathione metabolism
rkg00900  Terpenoid backbone biosynthesis
KO pathway
ko04216   
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