KEGG   PATHWAY: gvr04216
Entry
gvr04216                    Pathway                                
Name
Ferroptosis - Galeopterus variegatus (Sunda flying lemur)
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
gvr04216  Ferroptosis
gvr04216

Other DBs
GO: 0097707
Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103591104  SLC3A2; 4F2 cell-surface antigen heavy chain [KO:K06519]
103595416  SLC7A11; cystine/glutamate transporter [KO:K13869]
103591400  TP53; cellular tumor antigen p53 [KO:K04451]
103608308  GCLC; glutamate--cysteine ligase catalytic subunit [KO:K11204] [EC:6.3.2.2]
103600958  GCLM; glutamate--cysteine ligase regulatory subunit [KO:K11205]
103589300  glutathione synthetase-like isoform X1 [KO:K21456] [EC:6.3.2.3]
103589990  glutathione synthetase isoform X1 [KO:K21456] [EC:6.3.2.3]
103603492  LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, mitochondrial-like [KO:K05361] [EC:1.11.1.12]
103609293  ACSL3; long-chain-fatty-acid--CoA ligase 3 isoform X1 [KO:K01897] [EC:6.2.1.3]
103590057  ACSL6; long-chain-fatty-acid--CoA ligase 6 isoform X1 [KO:K01897] [EC:6.2.1.3]
103585646  ACSL4; long-chain-fatty-acid--CoA ligase 4 isoform X1 [KO:K01897] [EC:6.2.1.3]
103605585  ACSL1; long-chain-fatty-acid--CoA ligase 1 isoform X1 [KO:K01897] [EC:6.2.1.3]
103587704  ACSL5; LOW QUALITY PROTEIN: long-chain-fatty-acid--CoA ligase 5 [KO:K01897] [EC:6.2.1.3]
103586394  LPCAT3; lysophospholipid acyltransferase 5 [KO:K13515] [EC:2.3.1.23 2.3.1.-]
103588408  arachidonate 15-lipoxygenase [KO:K00460] [EC:1.13.11.33]
103596493  SAT1; diamine acetyltransferase 1 [KO:K00657] [EC:2.3.1.57]
103591402  SAT2; diamine acetyltransferase 2 [KO:K00657] [EC:2.3.1.57]
103597300  LOW QUALITY PROTEIN: inhibitor of carbonic anhydrase-like [KO:K14736]
103597302  serotransferrin-like [KO:K14736]
103603665  TFRC; transferrin receptor protein 1 [KO:K06503]
103610460  STEAP3; metalloreductase STEAP3 [KO:K10142] [EC:1.16.1.-]
103587506  SLC11A2; natural resistance-associated macrophage protein 2 isoform X1 [KO:K21398]
103597142  SLC39A8; zinc transporter ZIP8 [KO:K14714]
103598108  SLC39A14; zinc transporter ZIP14 isoform X1 [KO:K14720]
103592875  PCBP2; poly(rC)-binding protein 2 isoform X1 [KO:K13162]
103609062  SLC40A1; solute carrier family 40 member 1 [KO:K14685]
103585930  solute carrier family 40 member 1-like [KO:K14685]
103581182  ceruloplasmin-like [KO:K13624] [EC:1.16.3.1]
103603852  ceruloplasmin-like [KO:K13624] [EC:1.16.3.1]
103603855  CP; ceruloplasmin [KO:K13624] [EC:1.16.3.1]
103583217  poly(rC)-binding protein 1-like isoform X1 [KO:K12889]
103606271  poly(rC)-binding protein 1-like [KO:K12889]
103593226  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
103600889  LOW QUALITY PROTEIN: poly(rC)-binding protein 1-like [KO:K12889]
103604101  FTH1; ferritin heavy chain [KO:K00522] [EC:1.16.3.1]
103587778  FTL; LOW QUALITY PROTEIN: ferritin light chain [KO:K13625]
103581725  LOW QUALITY PROTEIN: microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
103589305  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
103598197  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
103605890  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
103601178  ATG7; ubiquitin-like modifier-activating enzyme ATG7 [KO:K08337]
103588322  NCOA4; nuclear receptor coactivator 4 isoform X1 [KO:K09289]
103595532  PRNP; major prion protein [KO:K05634]
103582640  heme oxygenase 1-like [KO:K00510] [EC:1.14.14.18]
103605520  HMOX1; heme oxygenase 1 [KO:K00510] [EC:1.14.14.18]
103605434  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
103589264  voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
103593579  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
103594370  FTMT; ferritin, mitochondrial [KO:K18495] [EC:1.16.3.1]
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
gvr00480  Glutathione metabolism
gvr00900  Terpenoid backbone biosynthesis
KO pathway
ko04216   
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