KEGG   PATHWAY: kmr04216
Entry
kmr04216                    Pathway                                
Name
Ferroptosis - Kryptolebias marmoratus (mangrove rivulus)
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
kmr04216  Ferroptosis
kmr04216

Other DBs
GO: 0097707
Organism
Kryptolebias marmoratus (mangrove rivulus) [GN:kmr]
Gene
108234876  slc3a2a; solute carrier family 3 member 2a [KO:K06519]
108249617  4F2 cell-surface antigen heavy chain [KO:K06519]
108240952  4F2 cell-surface antigen heavy chain [KO:K06519]
108249099  slc7a11; cystine/glutamate transporter [KO:K13869]
108233310  si:ch73-352p4.8; cystine/glutamate transporter isoform X1 [KO:K13869]
108228351  tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
108234128  gclc; glutamate--cysteine ligase catalytic subunit [KO:K11204] [EC:6.3.2.2]
108230575  gclm; glutamate--cysteine ligase regulatory subunit [KO:K11205]
108233054  gss; glutathione synthetase [KO:K21456] [EC:6.3.2.3]
108230562  gpx4a; glutathione peroxidase 4a [KO:K05361] [EC:1.11.1.12]
108239424  phospholipid hydroperoxide glutathione peroxidase-like isoform X1 [KO:K05361] [EC:1.11.1.12]
108249434  acsl5; long-chain-fatty-acid--CoA ligase 5 [KO:K01897] [EC:6.2.1.3]
108236528  acsl2; long-chain-fatty-acid--CoA ligase 1 [KO:K01897] [EC:6.2.1.3]
108230046  acsl1a; long-chain-fatty-acid--CoA ligase 1a isoform X1 [KO:K01897] [EC:6.2.1.3]
108238008  acsl4a; long-chain-fatty-acid--CoA ligase 4 [KO:K01897] [EC:6.2.1.3]
108240045  long-chain-fatty-acid--CoA ligase 1-like isoform X1 [KO:K01897] [EC:6.2.1.3]
108238091  acsl6; long-chain-fatty-acid--CoA ligase 6 [KO:K01897] [EC:6.2.1.3]
108250985  acsl3a; long-chain-fatty-acid--CoA ligase 3a [KO:K01897] [EC:6.2.1.3]
108245538  acsl3b; long-chain-fatty-acid--CoA ligase 3b [KO:K01897] [EC:6.2.1.3]
108235414  lpcat3; lysophospholipid acyltransferase 5 isoform X1 [KO:K13515] [EC:2.3.1.23 2.3.1.-]
108236911  diamine acetyltransferase 1-like [KO:K00657] [EC:2.3.1.57]
108245213  sat2b; diamine acetyltransferase 2b [KO:K00657] [EC:2.3.1.57]
108249538  diamine acetyltransferase 1 [KO:K00657] [EC:2.3.1.57]
108247767  thialysine N-epsilon-acetyltransferase [KO:K00657] [EC:2.3.1.57]
108239656  tfa; transferrin-a [KO:K14736]
108234733  tfr1b; transferrin receptor 1b [KO:K06503]
108238212  transferrin receptor protein 1-like [KO:K06503]
108238324  transferrin receptor protein 1-like [KO:K06503]
108249843  metalloreductase STEAP3 [KO:K10142] [EC:1.16.1.-]
108235664  slc11a2; natural resistance-associated macrophage protein 2 isoform X1 [KO:K21398]
108244526  slc39a14; metal cation symporter ZIP14 isoform X1 [KO:K14720]
108231599  poly(rC)-binding protein 2 isoform X1 [KO:K13162]
108232128  poly(rC)-binding protein 2 isoform X1 [KO:K13162]
108241961  si:ch211-254p10.2; solute carrier family 40 member 1 [KO:K14685]
108250771  slc40a1; solute carrier family 40 member 1 [KO:K14685]
108238449  ceruloplasmin [KO:K13624] [EC:1.16.3.1]
108229810  ferritin, heavy subunit [KO:K00522] [EC:1.16.3.1]
108229182  ferritin, middle subunit [KO:K00522] [EC:1.16.3.1]
108228815  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
108237261  zgc:56095; ferritin, lower subunit [KO:K00522] [EC:1.16.3.1]
108230209  fth1b; ferritin, heavy polypeptide 1b [KO:K00522] [EC:1.16.3.1]
108228605  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
108229683  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
108231304  map1lc3cl; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
108250086  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
108243242  atg5; autophagy protein 5 [KO:K08339]
108231482  atg7; ubiquitin-like modifier-activating enzyme ATG7 [KO:K08337]
108247336  ncoa4; nuclear receptor coactivator 4 [KO:K09289]
108244335  heme oxygenase [KO:K00510] [EC:1.14.14.18]
108236044  hmox1a; heme oxygenase 1a [KO:K00510] [EC:1.14.14.18]
108249683  voltage-dependent anion-selective channel protein 2-like [KO:K15040]
108245669  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
108247151  zgc:56235; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15041]
108233711  vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
108251269  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
kmr00480  Glutathione metabolism
kmr00900  Terpenoid backbone biosynthesis
KO pathway
ko04216   
LinkDB

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