Ferroptosis (WP4313)

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].
last edited

Authors

Khanspers, Egonw, MaintBot, DeSl, Finterly, and DanielL

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: ferroptosis pathway unsaturated fatty acid biosynthetic pathway cell death pathway mitochondrial disease pathway

Disease Ontology: epilepsy

Participants

Label Type Compact Identifier
PE-AA/PE-AdA Metabolite chebi:79110
Terpenoid backbonebiosynthesis Pathway None
CHMP5 GeneProduct ensembl:ENSG00000086065
Sorafenib Metabolite chebi:50924
COQ2 GeneProduct ensembl:ENSG00000173085
GSH Metabolite chebi:16856
Arachidonate Metabolite chebi:15843
CoA Metabolite chebi:15346
PCBP1 GeneProduct ensembl:ENSG00000169564
FDFT1 GeneProduct ensembl:ENSG00000079459
AKR1C1 GeneProduct ensembl:ENSG00000187134
Vitamin E Metabolite chebi:18145
heme Metabolite chebi:30413
FIN56 Metabolite chebi:176419
Methionine Metabolite chebi:16643
ACSL1 GeneProduct ensembl:ENSG00000151726
PHKG2 GeneProduct ensembl:ENSG00000156873
STEAP3 GeneProduct ensembl:ENSG00000115107
AIFM2 GeneProduct ensembl:ENSG00000042286
RSL3 Metabolite pubchem.compound:1750826
POR GeneProduct ensembl:ENSG00000127948
Erastin Metabolite pubchem.compound:11214940
VDAC2 GeneProduct ensembl:ENSG00000165637
PE-AA-OH/PE-AdA-OH Metabolite pubchem.compound:52929784
Fe3+ Metabolite chebi:29034
PRNP GeneProduct ensembl:ENSG00000171867
CHMP6 GeneProduct ensembl:ENSG00000176108
TF GeneProduct ensembl:ENSG00000091513
Arachidonyl-CoA Metabolite chebi:15514
ESCRT-III Complex reactome:R-HSA-917723
TXNRD1 GeneProduct ensembl:ENSG00000198431
NOX1 GeneProduct ensembl:ENSG00000007952
15-LO Protein uniprot:P16050
hydrogen peroxide Metabolite chebi:16240
HMG-CoA Metabolite chebi:15467
BH4 Metabolite chebi:15372
MAP1LC3B GeneProduct ensembl:ENSG00000140941
AKR1C3 GeneProduct ensembl:ENSG00000196139
GCLC GeneProduct ensembl:ENSG00000001084
Se Metabolite chebi:27568
CYBB GeneProduct ensembl:ENSG00000165168
squalene Metabolite chebi:15440
LysoPE Metabolite chebi:75036
Fe2+ Metabolite chebi:29033
SLC3A2 GeneProduct ensembl:ENSG00000168003
FTMT GeneProduct ensembl:ENSG00000181867
CoQ10 Metabolite chebi:46245
IREB2 GeneProduct ensembl:ENSG00000136381
CISD1 GeneProduct ensembl:ENSG00000122873
MAP1LC3C GeneProduct ensembl:ENSG00000197769
hydroxyl radical Metabolite chebi:29191
GCH1 GeneProduct ensembl:ENSG00000131979
SLC39A8 GeneProduct ensembl:ENSG00000138821
HSPB1 GeneProduct ensembl:ENSG00000106211
HMGCR GeneProduct ensembl:ENSG00000113161
(R)-Mevalonate Metabolite chebi:17710
ATG5 GeneProduct ensembl:ENSG00000057663
HMOX1 GeneProduct ensembl:ENSG00000100292
Acetyl-CoA Metabolite chebi:15351
glutamate Metabolite chebi:14321
Glutamine Metabolite chebi:18050
NOX2 GeneProduct ensembl:ENSG00000165168
Eicosanoid Metabolism via Lipo Oxygenases (LOX) Pathway wikipathways:WP4721
PCBP2 GeneProduct ensembl:ENSG00000197111
EPI-743 Metabolite wikidata:Q27265220
CTH GeneProduct ensembl:ENSG00000116761
DPP4 GeneProduct ensembl:ENSG00000197635
PUFA Metabolite lipidmaps:LMFA0103
IPP Metabolite chebi:128769
gamma-L-Glutamyl-L-cysteine Metabolite chebi:17515
CBS GeneProduct ensembl:ENSG00000160200
BACH1 GeneProduct ensembl:ENSG00000156273
FTH1 GeneProduct ensembl:ENSG00000167996
TFRC GeneProduct ensembl:ENSG00000072274
FIN56 Metabolite chebi:176419
NOX4 GeneProduct ensembl:ENSG00000086991
GPX4 GeneProduct ensembl:ENSG00000167468
SLC39A14 GeneProduct ensembl:ENSG00000104635
SLC40A1 GeneProduct ensembl:ENSG00000138449
SLC7A11 GeneProduct ensembl:ENSG00000151012
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
GCLM GeneProduct ensembl:ENSG00000023909
GSS GeneProduct ensembl:ENSG00000100983
GSSG Metabolite chebi:17858
PE-AA-O-OH/PE-AdA-O-OH Metabolite pubchem.compound:124222235
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
Fe3+ Metabolite chebi:29034
TF GeneProduct ensembl:ENSG00000091513
TFRC GeneProduct ensembl:ENSG00000072274
CP GeneProduct ensembl:ENSG00000047457
Fe2+ Metabolite chebi:29033
Fe3+ Metabolite chebi:29034
Fe2+ Metabolite chebi:29033
Fe2+ Metabolite chebi:29033
PCBP2 GeneProduct ensembl:ENSG00000197111
Fe3+ Metabolite chebi:29034
FTL GeneProduct ensembl:ENSG00000087086
NCOA4 GeneProduct ensembl:ENSG00000266412
FTH1 GeneProduct ensembl:ENSG00000167996
Fe3+ Metabolite chebi:29034
FTL GeneProduct ensembl:ENSG00000087086
MAP1LC3A GeneProduct ensembl:ENSG00000101460
ATG7 GeneProduct ensembl:ENSG00000197548
Fe3+ Metabolite chebi:29034
TF GeneProduct ensembl:ENSG00000091513
TFRC GeneProduct ensembl:ENSG00000072274
SLC11A2 GeneProduct ensembl:ENSG00000110911
SLC39A8 GeneProduct ensembl:ENSG00000138821
SLC39A14 GeneProduct ensembl:ENSG00000104635
Fe2+ Metabolite chebi:29033
VDAC3 GeneProduct ensembl:ENSG00000078668
Fe2+ Metabolite chebi:29033
Erastin Metabolite pubchem.compound:11214940
PUFA-OOH Metabolite lipidmaps:LMFA0306
PUFA-OH Metabolite lipidmaps:LMFA0105
Glutamine Metabolite chebi:18050
SLC1A5 GeneProduct ensembl:ENSG00000105281
SLC38A1 GeneProduct ensembl:ENSG00000111371
BACH1 GeneProduct ensembl:ENSG00000156273
AIFM2 GeneProduct ensembl:ENSG00000042286
AKR1C2 GeneProduct ensembl:ENSG00000151632

References

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