Ferroptosis (Homo sapiens)

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1, 75651131113113111AutolysomeEndosomeEndosomeMitochondriaFenton reaction(Non-TF bound iron)Transsulfuration PathwayFerritin degradationReleased ironROSSystem Xc-FerroptosisIron storage8CHMP6CBSIREB2SorafenibFTH1Fe2+DPP4hydroxyl radicalErastinAKR1C3hydrogen peroxideHSPB1CISD115-LONOX2gamma-L-Glutamyl-L-cysteineSLC39A8BH4ESCRT-III PE-AA/PE-AdAGCLCAcetyl-CoACTHATG5Arachidonyl-CoALysoPEVitamin EEPI-743HMOX1FIN56FTMTSLC39A14MAP1LC3CFe3+PE-AA-OH/PE-AdA-OHPCBP2TFRCCoQ10IPPCYBBMethioninehemeEicosanoid Metabolism via Lipo Oxygenases (LOX)SLC3A2MAP1LC3BGSHTXNRD1HMGCRNOX4GCH1PRNPHMG-CoATerpenoid backbonebiosynthesisAIFM2CoANOX1AKR1C1COQ2CHMP5PCBP1FIN56GlutamineRSL3STEAP3ArachidonatePHKG2TFPOR(R)-MevalonateACSL1VDAC2SLC40A1PUFASeglutamateBACH1squaleneFDFT1GPX441119853511SLC7A11312510416161213665105595glutamateSulfasalazineglutamatecystinecysteine (Cys)cystine1GCLM1GSSGSSG1PE-AA-O-OH/PE-AdA-O-OHALOX151SAT1SAT2TP53LPCAT3ACSL3ACSL4ACSL6ACSL5Fe3+TFTFRCCPFe2+Fe3+Fe2+Fe2+PCBP2Fe3+FTLNCOA4FTH1Fe3+FTLMAP1LC3AATG7Fe3+TFTFRCSLC11A2SLC39A8SLC39A14Fe2+VDAC3Fe2+ErastinPUFA-OOHPUFA-OH33Glutamine9SLC1A5SLC38A1BACH112AIFM26AKR1C2


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.

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  1. 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
  2. Friedmann Angeli JP, Krysko DV, Conrad M; ''''; , 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. Mou Y, Wang J, Wu J, He D, Zhang C, Duan C, Li B; ''Ferroptosis, a new form of cell death: opportunities and challenges in cancer.''; J Hematol Oncol, 2019 PubMed Europe PMC Scholia
  5. Tang D, Chen X, Kang R, Kroemer G; ''Ferroptosis: molecular mechanisms and health implications.''; Cell Res, 2021 PubMed Europe PMC Scholia
  6. Kuang F, Liu J, Tang D, Kang R; ''Oxidative Damage and Antioxidant Defense in Ferroptosis.''; Front Cell Dev Biol, 2020 PubMed Europe PMC Scholia
  7. ''Ferroptosis - Homo sapiens (human)''; https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa04216,
  8. Shen L, Lin D, Li X, Wu H, Lenahan C, Pan Y, Xu W, Chen Y, Shao A, Zhang J; ''Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?''; Front Cell Dev Biol, 2020 PubMed Europe PMC Scholia
  9. Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, Sun B, Wang G; ''Ferroptosis: past, present and future.''; Cell Death Dis, 2020 PubMed Europe PMC Scholia
  10. Han C, Liu Y, Dai R, Ismail N, Su W, Li B; ''Ferroptosis and Its Potential Role in Human Diseases.''; Front Pharmacol, 2020 PubMed Europe PMC Scholia
  11. 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
  12. Nishizawa H, Matsumoto M, Shindo T, Saigusa D, Kato H, Suzuki K, Sato M, Ishii Y, Shimokawa H, Igarashi K; ''Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1.''; J Biol Chem, 2020 PubMed Europe PMC Scholia
  13. Jiang X, Stockwell BR, Conrad M; ''Ferroptosis: mechanisms, biology and role in disease.''; Nat Rev Mol Cell Biol, 2021 PubMed Europe PMC Scholia


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123507view04:59, 29 July 2022EgonwMade a pathway clickable
122998view11:12, 13 June 2022DanielLFIN56 modified to be a direct activator of FDFT1 in the mevalonate pathway according to literature
120500view12:39, 9 December 2021DanielLadded NOXs and DPP4 that stimulate ROS production
120452view13:15, 3 December 2021DanielLfixed unlinked interaction
120440view13:18, 2 December 2021DanielL*Added the AKR1C family
  • Added HMGCR, FDFT1 and FIN56 as elements that influence the squalene biosynthesis pathway
120432view14:06, 1 December 2021DanielL*Added GCH1 and BH4
120431view13:02, 1 December 2021DanielLAdded CTH/CBS (mediators in the transsulfurination pathway) Added the ESCRT-III machinery
120423view14:10, 30 November 2021DanielL*Added POR and NOX1
120366view12:20, 29 November 2021DanielLAdded AIFM2(FSP1) and COQ2 as part of the CoQ10 antiferroptotic system
120033view07:55, 18 October 2021DanielLAdded BACH1
120016view13:09, 14 October 2021DanielLungrouping of PHKG2 from IREB2, CISD1 from HSPB1 and FIN56 from RSL3
119996view07:16, 9 October 2021EgonwNot a conversion
119993view13:47, 8 October 2021DanielLAdded CISD1 (supressor of Fe2+)

Added PHKG2 (promoter of Fe2+)

Added Squalene as an inhibitor of ferroptosis
119973view13:31, 5 October 2021DanielL* Added the glutamine metabolic pathway
  • Added IREB 2, PKC and HSPB1 in relationship with Fe2+
  • Added TXNRD1
With their respective references
119965view15:23, 3 October 2021DanielL*Added FIN56 as an inhibitor to GPX4
  • Added the transulfuration pathway (that can inhibit ferroptosis via cystine deprivation)
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


View all...
NameTypeDatabase referenceComment
(R)-MevalonateMetaboliteCHEBI:17710 (ChEBI)
15-LOProteinP16050 (Uniprot-TrEMBL) aka 15-lipoxygenase (EC; ALOX15
ACSL1GeneProductENSG00000151726 (Ensembl)
ACSL3GeneProductENSG00000123983 (Ensembl)
ACSL4GeneProductENSG00000068366 (Ensembl)
ACSL5GeneProductENSG00000197142 (Ensembl)
ACSL6GeneProductENSG00000164398 (Ensembl)
AIFM2GeneProductENSG00000042286 (Ensembl)
AKR1C1GeneProductENSG00000187134 (Ensembl)
AKR1C2GeneProductENSG00000151632 (Ensembl)
AKR1C3GeneProductENSG00000196139 (Ensembl)
ALOX15GeneProductALOX15 (HGNC)
ATG5GeneProductENSG00000057663 (Ensembl)
ATG7GeneProductENSG00000197548 (Ensembl)
Acetyl-CoAMetaboliteCHEBI:15351 (ChEBI)
ArachidonateMetaboliteCHEBI:15843 (ChEBI)
Arachidonyl-CoAMetaboliteCHEBI:15514 (ChEBI)
BACH1GeneProductENSG00000156273 (Ensembl)
BH4MetaboliteCHEBI:15372 (ChEBI)
CBSGeneProductENSG00000160200 (Ensembl)
CHMP5GeneProductENSG00000086065 (Ensembl)
CHMP6GeneProductENSG00000176108 (Ensembl)
CISD1GeneProductENSG00000122873 (Ensembl)
COQ2GeneProductENSG00000173085 (Ensembl)
CPGeneProductENSG00000047457 (Ensembl)
CTHGeneProductENSG00000116761 (Ensembl)
CYBBGeneProductENSG00000165168 (Ensembl)
CoAMetaboliteCHEBI:15346 (ChEBI)
CoQ10MetaboliteCHEBI:46245 (ChEBI)
DPP4GeneProductENSG00000197635 (Ensembl)
EPI-743MetaboliteQ27265220 (Wikidata) aka vatiquinone (α-tocotrienol quinone)
ESCRT-III ComplexR-HSA-917723 (Reactome)


via Lipo 
Oxygenases (LOX)
PathwayWP4721 (WikiPathways)
ErastinMetabolite11214940 (PubChem-compound)
FDFT1GeneProductENSG00000079459 (Ensembl)
FIN56MetaboliteCHEBI:176419 (ChEBI)
FTH1GeneProductENSG00000167996 (Ensembl)
FTLGeneProductENSG00000087086 (Ensembl)
FTMTGeneProductENSG00000181867 (Ensembl)
Fe2+MetaboliteCHEBI:29033 (ChEBI)
Fe3+MetaboliteCHEBI:29034 (ChEBI)
GCH1GeneProductENSG00000131979 (Ensembl)
GCLCGeneProductENSG00000001084 (Ensembl)
GCLMGeneProductENSG00000023909 (Ensembl)
GPX4GeneProductENSG00000167468 (Ensembl)
GSHMetaboliteCHEBI:16856 (ChEBI) Glutathione
GSSGeneProductENSG00000100983 (Ensembl)
GSSGMetaboliteCHEBI:17858 (ChEBI)
GlutamineMetaboliteCHEBI:18050 (ChEBI)
HMG-CoAMetaboliteCHEBI:15467 (ChEBI)
HMGCRGeneProductENSG00000113161 (Ensembl)
HMOX1GeneProductENSG00000100292 (Ensembl)
HSPB1GeneProductENSG00000106211 (Ensembl)
IPPMetaboliteCHEBI:128769 (ChEBI)
IREB2GeneProductENSG00000136381 (Ensembl)
LPCAT3GeneProductENSG00000111684 (Ensembl)
LysoPEMetaboliteCHEBI:75036 (ChEBI)
MAP1LC3AGeneProductENSG00000101460 (Ensembl)
MAP1LC3BGeneProductENSG00000140941 (Ensembl)
MAP1LC3CGeneProductENSG00000197769 (Ensembl)
MethionineMetaboliteCHEBI:16643 (ChEBI)
NCOA4GeneProductENSG00000266412 (Ensembl)
NOX1GeneProductENSG00000007952 (Ensembl)
NOX2GeneProductENSG00000165168 (Ensembl)
NOX4GeneProductENSG00000086991 (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)
PHKG2GeneProductENSG00000156873 (Ensembl)
PORGeneProductENSG00000127948 (Ensembl)
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)
SLC1A5GeneProductENSG00000105281 (Ensembl)
SLC38A1GeneProductENSG00000111371 (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)
TXNRD1GeneProductENSG00000198431 (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)
squaleneMetaboliteCHEBI:15440 (ChEBI)

Annotated Interactions

No annotated interactions

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