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].
Authors
Kristina Hanspers , Egon Willighagen , Denise Slenter , Finterly Hu , and Daniel-Alexandru LupascuActivity
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Cited In
- Blood biomarkers representing maternal-fetal interface tissues used to predict early-and late-onset preeclampsia but not COVID-19 infection (2022).
- Ferroptosis-Related Long Non-Coding RNA Signature Contributes to the Prediction of Prognosis Outcomes in Head and Neck Squamous Cell Carcinomas (2021).
- Selenotranscriptome Network in Non-alcoholic Fatty Liver Disease (2021).
- The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Glutathione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression (2021).
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
ferroptosis pathway mitochondrial disease pathway cell death pathway unsaturated fatty acid biosynthetic pathwayDisease Ontology
epilepsy| 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 1.13.11.33); ALOX15 |
References
- KEGG Pathway: hsa04216
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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