Ferroptosis (WP4313)

Homo sapiens

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 [https://www.genome.jp/dbget-bin/www_bget?pathway+hsa04216 KEGG] and [https://en.wikipedia.org/wiki/Ferroptosis Wikipedia].


Kristina Hanspers , Egon Willighagen , Denise Slenter , Finterly Hu , and Daniel-Alexandru Lupascu


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Homo sapiens



Pathway Ontology

ferroptosis pathway mitochondrial disease pathway cell death pathway unsaturated fatty acid biosynthetic pathway

Disease Ontology



Label Type Compact URI Comment
PE-AA/PE-AdA Metabolite chebi:79110
Sorafenib Metabolite chebi:50924
GSH Metabolite chebi:16856 Glutathione
Arachidonate Metabolite chebi:15843
CoA Metabolite chebi:15346
Vitamin E Metabolite chebi:18145
heme Metabolite chebi:30413
FIN56 Metabolite chebi:176419
Methionine Metabolite chebi:16643
RSL3 Metabolite pubchem.compound:1750826
Erastin Metabolite pubchem.compound:11214940
PE-AA-OH/PE-AdA-OH Metabolite pubchem.compound:52929784 aka LOOH
Fe3+ Metabolite chebi:29034
Arachidonyl-CoA Metabolite chebi:15514
hydrogen peroxide Metabolite chebi:16240
HMG-CoA Metabolite chebi:15467
BH4 Metabolite chebi:15372
Se Metabolite chebi:27568
squalene Metabolite chebi:15440
LysoPE Metabolite chebi:75036
Fe2+ Metabolite chebi:29033
CoQ10 Metabolite chebi:46245
hydroxyl radical Metabolite chebi:29191
(R)-Mevalonate Metabolite chebi:17710
Acetyl-CoA Metabolite chebi:15351
glutamate Metabolite chebi:14321
Glutamine Metabolite chebi:18050
EPI-743 Metabolite wikidata:Q27265220 aka vatiquinone (α-tocotrienol quinone)
PUFA Metabolite lipidmaps:LMFA0103 aka Poly Unsaturated Fatty Acid
IPP Metabolite chebi:128769
gamma-L-Glutamyl-L-cysteine Metabolite chebi:17515
FIN56 Metabolite chebi:176419
glutamate Metabolite chebi:14321
Sulfasalazine Metabolite chebi:9334
glutamate Metabolite chebi:14321
cystine Metabolite chebi:35492
cysteine (Cys) Metabolite chebi:15356
cystine Metabolite chebi:35492
GSSG Metabolite chebi:17858
PE-AA-O-OH/PE-AdA-O-OH Metabolite pubchem.compound:124222235 aka LOOH
Fe3+ Metabolite chebi:29034
Fe2+ Metabolite chebi:29033
Fe3+ Metabolite chebi:29034
Fe2+ Metabolite chebi:29033
Fe2+ Metabolite chebi:29033
Fe3+ Metabolite chebi:29034
Fe3+ Metabolite chebi:29034
Fe3+ Metabolite chebi:29034
Fe2+ Metabolite chebi:29033
Fe2+ Metabolite chebi:29033
Erastin Metabolite pubchem.compound:11214940
PUFA-OOH Metabolite lipidmaps:LMFA0306 aka Poly Unsaturated Fatty Acid
PUFA-OH Metabolite lipidmaps:LMFA0105 aka Poly Unsaturated Fatty Acid
Glutamine Metabolite chebi:18050
CHMP5 GeneProduct ensembl:ENSG00000086065
COQ2 GeneProduct ensembl:ENSG00000173085
PCBP1 GeneProduct ensembl:ENSG00000169564
FDFT1 GeneProduct ensembl:ENSG00000079459
AKR1C1 GeneProduct ensembl:ENSG00000187134
ACSL1 GeneProduct ensembl:ENSG00000151726
PHKG2 GeneProduct ensembl:ENSG00000156873
STEAP3 GeneProduct ensembl:ENSG00000115107
AIFM2 GeneProduct ensembl:ENSG00000042286
POR GeneProduct ensembl:ENSG00000127948
VDAC2 GeneProduct ensembl:ENSG00000165637
PRNP GeneProduct ensembl:ENSG00000171867
CHMP6 GeneProduct ensembl:ENSG00000176108
TF GeneProduct ensembl:ENSG00000091513
TXNRD1 GeneProduct ensembl:ENSG00000198431
NOX1 GeneProduct ensembl:ENSG00000007952
MAP1LC3B GeneProduct ensembl:ENSG00000140941
AKR1C3 GeneProduct ensembl:ENSG00000196139
GCLC GeneProduct ensembl:ENSG00000001084
CYBB GeneProduct ensembl:ENSG00000165168
SLC3A2 GeneProduct ensembl:ENSG00000168003
FTMT GeneProduct ensembl:ENSG00000181867
IREB2 GeneProduct ensembl:ENSG00000136381
CISD1 GeneProduct ensembl:ENSG00000122873
MAP1LC3C GeneProduct ensembl:ENSG00000197769
GCH1 GeneProduct ensembl:ENSG00000131979
SLC39A8 GeneProduct ensembl:ENSG00000138821
HSPB1 GeneProduct ensembl:ENSG00000106211
HMGCR GeneProduct ensembl:ENSG00000113161
ATG5 GeneProduct ensembl:ENSG00000057663
HMOX1 GeneProduct ensembl:ENSG00000100292
NOX2 GeneProduct ensembl:ENSG00000165168
PCBP2 GeneProduct ensembl:ENSG00000197111
CTH GeneProduct ensembl:ENSG00000116761
DPP4 GeneProduct ensembl:ENSG00000197635
CBS GeneProduct ensembl:ENSG00000160200
BACH1 GeneProduct ensembl:ENSG00000156273
FTH1 GeneProduct ensembl:ENSG00000167996
TFRC GeneProduct ensembl:ENSG00000072274
NOX4 GeneProduct ensembl:ENSG00000086991
GPX4 GeneProduct ensembl:ENSG00000167468
SLC39A14 GeneProduct ensembl:ENSG00000104635
SLC40A1 GeneProduct ensembl:ENSG00000138449
SLC7A11 GeneProduct ensembl:ENSG00000151012
GCLM GeneProduct ensembl:ENSG00000023909
GSS GeneProduct ensembl:ENSG00000100983
ALOX15 GeneProduct hgnc.symbol:ALOX15
SAT1 GeneProduct ensembl:ENSG00000130066
SAT2 GeneProduct ensembl:ENSG00000141504
TP53 GeneProduct ensembl:ENSG00000141510
LPCAT3 GeneProduct ensembl:ENSG00000111684
ACSL3 GeneProduct ensembl:ENSG00000123983
ACSL4 GeneProduct ensembl:ENSG00000068366
ACSL6 GeneProduct ensembl:ENSG00000164398
ACSL5 GeneProduct ensembl:ENSG00000197142
TF GeneProduct ensembl:ENSG00000091513
TFRC GeneProduct ensembl:ENSG00000072274
CP GeneProduct ensembl:ENSG00000047457
PCBP2 GeneProduct ensembl:ENSG00000197111
FTL GeneProduct ensembl:ENSG00000087086
NCOA4 GeneProduct ensembl:ENSG00000266412
FTH1 GeneProduct ensembl:ENSG00000167996
FTL GeneProduct ensembl:ENSG00000087086
MAP1LC3A GeneProduct ensembl:ENSG00000101460
ATG7 GeneProduct ensembl:ENSG00000197548
TF GeneProduct ensembl:ENSG00000091513
TFRC GeneProduct ensembl:ENSG00000072274
SLC11A2 GeneProduct ensembl:ENSG00000110911
SLC39A8 GeneProduct ensembl:ENSG00000138821
SLC39A14 GeneProduct ensembl:ENSG00000104635
VDAC3 GeneProduct ensembl:ENSG00000078668
SLC1A5 GeneProduct ensembl:ENSG00000105281
SLC38A1 GeneProduct ensembl:ENSG00000111371
BACH1 GeneProduct ensembl:ENSG00000156273
AIFM2 GeneProduct ensembl:ENSG00000042286
AKR1C2 GeneProduct ensembl:ENSG00000151632
15-LO Protein uniprot:P16050 aka 15-lipoxygenase (EC; ALOX15


  1. KEGG Pathway: hsa04216
  2. Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration. Abdalkader M, Lampinen R, Kanninen KM, Malm TM, Liddell JR. Front Neurosci. 2018 Jul 10;12:466. PubMed Europe PMC Scholia
  3. Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. Hinman A, Holst CR, Latham JC, Bruegger JJ, Ulas G, McCusker KP, et al. PLoS One. 2018 Aug 15;13(8):e0201369. PubMed Europe PMC Scholia
  4. Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy. Kahn-Kirby AH, Amagata A, Maeder CI, Mei JJ, Sideris S, Kosaka Y, et al. PLoS One. 2019 Mar 28;14(3):e0214250. PubMed Europe PMC Scholia
  5. Ferroptosis, a new form of cell death: opportunities and challenges in cancer. Mou Y, Wang J, Wu J, He D, Zhang C, Duan C, et al. J Hematol Oncol. 2019 Mar 29;12(1):34. PubMed Europe PMC Scholia
  6. Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Friedmann Angeli JP, Krysko DV, Conrad M. Nat Rev Cancer. 2019 Jul;19(7):405–14. PubMed Europe PMC Scholia
  7. Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1. Nishizawa H, Matsumoto M, Shindo T, Saigusa D, Kato H, Suzuki K, et al. J Biol Chem. 2020 Jan 3;295(1):69–82. PubMed Europe PMC Scholia
  8. Ferroptosis: past, present and future. Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, et al. Cell Death Dis. 2020 Feb 3;11(2):88. PubMed Europe PMC Scholia
  9. Ferroptosis and Its Potential Role in Human Diseases. Han C, Liu Y, Dai R, Ismail N, Su W, Li B. Front Pharmacol. 2020 Mar 17;11:239. PubMed Europe PMC Scholia
  10. Ferroptosis in Acute Central Nervous System Injuries: The Future Direction? Shen L, Lin D, Li X, Wu H, Lenahan C, Pan Y, et al. Front Cell Dev Biol. 2020 Jul 15;8:594. PubMed Europe PMC Scholia
  11. Oxidative Damage and Antioxidant Defense in Ferroptosis. Kuang F, Liu J, Tang D, Kang R. Front Cell Dev Biol. 2020 Sep 17;8:586578. PubMed Europe PMC Scholia
  12. Ferroptosis: molecular mechanisms and health implications. Tang D, Chen X, Kang R, Kroemer G. Cell Res. 2021 Feb;31(2):107–25. PubMed Europe PMC Scholia
  13. Ferroptosis: mechanisms, biology and role in disease. Jiang X, Stockwell BR, Conrad M. Nat Rev Mol Cell Biol. 2021 Apr;22(4):266–82. PubMed Europe PMC Scholia