Ferroptosis (Homo sapiens)

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1, 223222442233MitochondriaEndosomeAutolysomeEndosomeROS(Non-TF bound iron)Iron storageFenton reactionSystem Xc-Ferritin degradationReleased ironFerroptosisSorafenibFTMTTFRCFe3+SLC3A2TFGPX4HMOX1MAP1LC3CPE-AA-OH/PE-AdA-OHCYBBPRNPPUFAEicosanoid Metabolism via Lipo Oxygenases (LOX)HMG-CoAEPI-743ATG5CoQ10GSHSLC40A1ArachidonateRSL3STEAP3VDAC2LysoPEheme15-LOFTH1CoAIPPgamma-L-Glutamyl-L-cysteinePCBP2MAP1LC3BFe2+SePE-AA/PE-AdAhydroxyl radicalSLC39A8ACSL1SLC39A14(R)-MevalonateArachidonyl-CoAhydrogen peroxideVitamin EPCBP1Terpenoid backbonebiosynthesisGCLCAcetyl-CoAErastin23223SLC7A112422glutamateSulfasalazineglutamatecystinecysteine (Cys)cystine2GCLM2GSSGSSGPE-AA-O-OH/PE-AdA-O-OH2ALOX152SAT1SAT2TP53LPCAT3ACSL3ACSL4ACSL6ACSL5Fe3+TFTFRCCPFe2+Fe3+Fe2+Fe2+PCBP2Fe3+FTLNCOA4FTH1Fe3+FTLMAP1LC3AATG7Fe3+TFTFRCSLC11A2SLC39A8SLC39A14Fe2+VDAC3Fe2+ErastinPUFA-OOHPUFA-OH33


Description

Ferroptosis is a type of programmed cell death which is distinct from apoptosis and necrosis, since cell death occurs due to failure of the glutathione-dependent antioxidant defenses in regulating iron. Reactive oxygen species (ROS) are produced from accumulated iron and lipid peroxidation (regulated by GrX4 and 15-LO).

Ferroptosis is important in several physiological and pathological processes, including cancer cell death, mitochondrial dysfunction induced epilepsy and neurodegenerative disease. Ferroptosis can be induced to treat multiple forms of cancer by inhibiting tumor growth, although the exact mechanism is unknown. Ferroptosis has also been linked to neurodegenerative disease, possibly through increased inflammation caused by release of lipid metabolites.

Description adapted from KEGG and Wikipedia.

Quality Tags

Ontology Terms

 

Bibliography

  1. ''Ferroptosis - Homo sapiens (human)''; https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa04216,
  2. Abdalkader M, Lampinen R, Kanninen KM, Malm TM, Liddell JR; ''Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration.''; Front Neurosci, 2018 PubMed Europe PMC Scholia
  3. Hinman A, Holst CR, Latham JC, Bruegger JJ, Ulas G, McCusker KP, Amagata A, Davis D, Hoff KG, Kahn-Kirby AH, Kim V, Kosaka Y, Lee E, Malone SA, Mei JJ, Richards SJ, Rivera V, Miller G, Trimmer JK, Shrader WD; ''''; , PubMed Europe PMC Scholia
  4. Kahn-Kirby AH, Amagata A, Maeder CI, Mei JJ, Sideris S, Kosaka Y, Hinman A, Malone SA, Bruegger JJ, Wang L, Kim V, Shrader WD, Hoff KG, Latham JC, Ashley EA, Wheeler MT, Bertini E, Carrozzo R, Martinelli D, Dionisi-Vici C, Chapman KA, Enns GM, Gahl W, Wolfe L, Saneto RP, Johnson SC, Trimmer JK, Klein MB, Holst CR; ''Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy.''; PLoS One, 2019 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
119231view18:56, 22 June 2021Finterlyadded KEGG biopax information
113766view17:18, 19 November 2020EgonwCompleted the LIPID MAPS identifiers.
112143view13:08, 28 September 2020DeSlOntology Term : 'epilepsy' added !
112142view13:08, 28 September 2020DeSlOntology Term : 'mitochondrial disease pathway' added !
112141view13:08, 28 September 2020DeSlOntology Term : 'unsaturated fatty acid biosynthetic pathway' added !
112140view13:07, 28 September 2020DeSlupdated description with info from recently added papers.
112139view13:04, 28 September 2020DeSlAdded EPI-743 with lit. ref
112138view12:58, 28 September 2020DeSlAdded PW ID to eicosanoid LOX PW.
112137view12:56, 28 September 2020DeSlAdded class IDs for PUFA, PUFA-OOh and PUFA-OH.
112136view12:53, 28 September 2020DeSlAdded info from Fig. 7 out of PMID:30110365
112135view12:32, 28 September 2020DeSlAdded details from fig. 1 of PMID: 30042655
107168view14:25, 17 September 2019MaintBotChEBI identifier normalization
106522view23:43, 5 September 2019KhanspersModified description
104979view19:13, 27 June 2019KhanspersModified description
101758view18:38, 5 November 2018Khanspersupdated xrefs for metabolites
97956view12:54, 26 June 2018EgonwAdded a title for the KEGG reference.
97955view12:51, 26 June 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
97941view20:34, 25 June 2018Khanspersfixed lit ref
97940view20:34, 25 June 2018Khanspersedited lit ref
97939view20:32, 25 June 2018KhanspersAdded KEGG as lit ref
97938view20:31, 25 June 2018KhanspersModified description
97936view20:12, 25 June 2018KhanspersModified description
97935view20:12, 25 June 2018KhanspersAdded selenium and fixed incorrect reaction
97909view15:07, 23 June 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
97908view19:33, 22 June 2018KhanspersModified description
97907view19:32, 22 June 2018KhanspersModified description
97906view19:29, 22 June 2018KhanspersOntology Term : 'cell death pathway' added !
97905view19:28, 22 June 2018KhanspersOntology Term : 'ferroptosis pathway' added !
97904view19:27, 22 June 2018KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(R)-MevalonateMetaboliteCHEBI:17710 (ChEBI)
15-LOProteinP16050 (Uniprot-TrEMBL) aka 15-lipoxygenase (EC 1.13.11.33); ALOX15
ACSL1GeneProductENSG00000151726 (Ensembl)
ACSL3GeneProductENSG00000123983 (Ensembl)
ACSL4GeneProductENSG00000068366 (Ensembl)
ACSL5GeneProductENSG00000197142 (Ensembl)
ACSL6GeneProductENSG00000164398 (Ensembl)
ALOX15GeneProductALOX15 (HGNC)
ATG5GeneProductENSG00000057663 (Ensembl)
ATG7GeneProductENSG00000197548 (Ensembl)
Acetyl-CoAMetaboliteCHEBI:15351 (ChEBI)
ArachidonateMetaboliteCHEBI:15843 (ChEBI)
Arachidonyl-CoAMetaboliteCHEBI:15514 (ChEBI)
CPGeneProductENSG00000047457 (Ensembl)
CYBBGeneProductENSG00000165168 (Ensembl)
CoAMetaboliteCHEBI:15346 (ChEBI)
CoQ10MetaboliteCHEBI:46245 (ChEBI)
EPI-743MetaboliteQ27265220 (Wikidata) aka vatiquinone (α-tocotrienol quinone)
Eicosanoid

Metabolism

via Lipo 
Oxygenases (LOX)
PathwayWP4721 (WikiPathways)
ErastinMetabolite11214940 (PubChem-compound)
FTH1GeneProductENSG00000167996 (Ensembl)
FTLGeneProductENSG00000087086 (Ensembl)
FTMTGeneProductENSG00000181867 (Ensembl)
Fe2+MetaboliteCHEBI:29033 (ChEBI)
Fe3+MetaboliteCHEBI:29034 (ChEBI)
GCLCGeneProductENSG00000001084 (Ensembl)
GCLMGeneProductENSG00000023909 (Ensembl)
GPX4GeneProductENSG00000167468 (Ensembl)
GSHMetaboliteCHEBI:16856 (ChEBI) Glutathione
GSSGeneProductENSG00000100983 (Ensembl)
GSSGMetaboliteCHEBI:17858 (ChEBI)
HMG-CoAMetaboliteCHEBI:15467 (ChEBI)
HMOX1GeneProductENSG00000100292 (Ensembl)
IPPMetaboliteCHEBI:128769 (ChEBI)
LPCAT3GeneProductENSG00000111684 (Ensembl)
LysoPEMetaboliteCHEBI:75036 (ChEBI)
MAP1LC3AGeneProductENSG00000101460 (Ensembl)
MAP1LC3BGeneProductENSG00000140941 (Ensembl)
MAP1LC3CGeneProductENSG00000197769 (Ensembl)
NCOA4GeneProductENSG00000266412 (Ensembl)
PCBP1GeneProductENSG00000169564 (Ensembl)
PCBP2GeneProductENSG00000197111 (Ensembl)
PE-AA-O-OH/ PE-AdA-O-OHMetabolite124222235 (PubChem-compound) aka LOOH
PE-AA-OH/ PE-AdA-OHMetabolite52929784 (PubChem-compound) aka LOOH
PE-AA/ PE-AdAMetaboliteCHEBI:79110 (ChEBI)
PRNPGeneProductENSG00000171867 (Ensembl)
PUFA-OHMetaboliteLMFA0105 (LIPID MAPS) aka Poly Unsaturated Fatty Acid
PUFA-OOHMetaboliteLMFA0306 (LIPID MAPS) aka Poly Unsaturated Fatty Acid
PUFAMetaboliteLMFA0103 (LIPID MAPS) aka Poly Unsaturated Fatty Acid
RSL3Metabolite1750826 (PubChem-compound)
SAT1GeneProductENSG00000130066 (Ensembl)
SAT2GeneProductENSG00000141504 (Ensembl)
SLC11A2GeneProductENSG00000110911 (Ensembl)
SLC39A14GeneProductENSG00000104635 (Ensembl)
SLC39A8GeneProductENSG00000138821 (Ensembl)
SLC3A2GeneProductENSG00000168003 (Ensembl)
SLC40A1GeneProductENSG00000138449 (Ensembl)
SLC7A11GeneProductENSG00000151012 (Ensembl)
STEAP3GeneProductENSG00000115107 (Ensembl)
SeMetaboliteCHEBI:27568 (ChEBI)
SorafenibMetaboliteCHEBI:50924 (ChEBI)
SulfasalazineMetaboliteCHEBI:9334 (ChEBI)
TFGeneProductENSG00000091513 (Ensembl)
TFRCGeneProductENSG00000072274 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
Terpenoid backbone biosynthesisPathway
VDAC2GeneProductENSG00000165637 (Ensembl)
VDAC3GeneProductENSG00000078668 (Ensembl)
Vitamin EMetaboliteCHEBI:18145 (ChEBI)
cysteine (Cys)MetaboliteCHEBI:15356 (ChEBI)
cystineMetaboliteCHEBI:35492 (ChEBI)
gamma-L-Glutamyl -L-cysteineMetaboliteCHEBI:17515 (ChEBI)
glutamateMetaboliteCHEBI:14321 (ChEBI)
hemeMetaboliteCHEBI:30413 (ChEBI)
hydrogen peroxideMetaboliteCHEBI:16240 (ChEBI)
hydroxyl radicalMetaboliteCHEBI:29191 (ChEBI)

Annotated Interactions

No annotated interactions

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