KEGG   PATHWAY: hsa04216
Entry
hsa04216                    Pathway                                
Name
Ferroptosis - Homo sapiens (human)
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
hsa04216  Ferroptosis
hsa04216

Network
nt06026  Glutathione biosynthesis
nt06525  Ferroptosis
  Element
N01587  Fe-TF transport
N01588  Fe3+ Ferritin transport
N01589  Glutathione biosynthesis
N01590  Arachidonate/Adrenic acid metabolism
N01591  Fe2+ Ferroportin transport
Drug
D11812  Pabinafusp alfa (genetical recombination) (JAN)
D12289  Vamifeport (USAN/INN)
D12290  Vamifeport trihydrochloride (USAN)
D12509  Trontinemab (USAN/INN)
D12510  Utreloxastat (JAN/USAN/INN)
D12806  Tividenofusp alfa (USAN/INN)
Other DBs
GO: 0097707
Organism
Homo sapiens (human) [GN:hsa]
Gene
10162  LPCAT3; lysophosphatidylcholine acyltransferase 3 [KO:K13515] [EC:2.3.1.23 2.3.1.-]
10533  ATG7; autophagy related 7 [KO:K08337]
112483  SAT2; spermidine/spermine N1-acetyltransferase family member 2 [KO:K00657] [EC:2.3.1.57]
1356  CP; ceruloplasmin [KO:K13624] [EC:1.16.3.1]
1536  CYBB; cytochrome b-245 beta chain [KO:K21421] [EC:1.-.-.-]
2180  ACSL1; acyl-CoA synthetase long chain family member 1 [KO:K01897] [EC:6.2.1.3]
2181  ACSL3; acyl-CoA synthetase long chain family member 3 [KO:K01897] [EC:6.2.1.3]
2182  ACSL4; acyl-CoA synthetase long chain family member 4 [KO:K01897] [EC:6.2.1.3]
23305  ACSL6; acyl-CoA synthetase long chain family member 6 [KO:K01897] [EC:6.2.1.3]
23516  SLC39A14; solute carrier family 39 member 14 [KO:K14720]
23657  SLC7A11; solute carrier family 7 member 11 [KO:K13869]
246  ALOX15; arachidonate 15-lipoxygenase [KO:K00460] [EC:1.13.11.33]
2495  FTH1; ferritin heavy chain 1 [KO:K00522] [EC:1.16.3.1]
2512  FTL; ferritin light chain [KO:K13625]
2729  GCLC; glutamate-cysteine ligase catalytic subunit [KO:K11204] [EC:6.3.2.2]
2730  GCLM; glutamate-cysteine ligase modifier subunit [KO:K11205]
2879  GPX4; glutathione peroxidase 4 [KO:K05361] [EC:1.11.1.12]
2937  GSS; glutathione synthetase [KO:K21456] [EC:6.3.2.3]
30061  SLC40A1; solute carrier family 40 member 1 [KO:K14685]
3162  HMOX1; heme oxygenase 1 [KO:K00510] [EC:1.14.14.18]
392288  MAP1LC3BP1; microtubule associated protein 1 light chain 3 beta pseudogene 1 [KO:K10435]
440738  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
4891  SLC11A2; solute carrier family 11 member 2 [KO:K21398]
5093  PCBP1; poly(rC) binding protein 1 [KO:K12889]
5094  PCBP2; poly(rC) binding protein 2 [KO:K13162]
51703  ACSL5; acyl-CoA synthetase long chain family member 5 [KO:K01897] [EC:6.2.1.3]
55240  STEAP3; STEAP3 metalloreductase [KO:K10142] [EC:1.16.1.-]
5621  PRNP; prion protein (Kanno blood group) [KO:K05634]
6303  SAT1; spermidine/spermine N1-acetyltransferase 1 [KO:K00657] [EC:2.3.1.57]
64116  SLC39A8; solute carrier family 39 member 8 [KO:K14714]
643246  MAP1LC3B2; microtubule associated protein 1 light chain 3 beta 2 [KO:K10435]
6520  SLC3A2; solute carrier family 3 member 2 [KO:K06519]
7018  TF; transferrin [KO:K14736]
7037  TFRC; transferrin receptor [KO:K06503]
7157  TP53; tumor protein p53 [KO:K04451]
7417  VDAC2; voltage dependent anion channel 2 [KO:K15040]
7419  VDAC3; voltage dependent anion channel 3 [KO:K15041]
8031  NCOA4; nuclear receptor coactivator 4 [KO:K09289]
81631  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
84557  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
94033  FTMT; ferritin mitochondrial [KO:K18495] [EC:1.16.3.1]
9474  ATG5; autophagy related 5 [KO:K08339]
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
hsa00480  Glutathione metabolism
hsa00900  Terpenoid backbone biosynthesis
KO pathway
ko04216   

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