Table 2.
Genes involved in ferroptosis
| Gene | Name | Funtion | Ref. | |
|---|---|---|---|---|
| Antioxidant defense | GPX4 | glutathione peroxidase 4 | Reduces lipid ROS with the aid of GSH | [1] |
| FSP1 | ferroptosis suppressor protein 1 | Reduces lipid peroxidation mediated by ubiquinone (CoQ10) | [109,125] | |
| GCH1 | GTP Cyclohydrolase 1 | Prevents lipid peroxidation by its metabolic derivatives BH4/BH2 | [126] | |
| FANCD2 | Fanconi anemia complementation group D2 | Regulats ferroptosis by affacting GPX4 expression | [127] | |
| Peroxidation | ALOXs | lipoxygenases | Directly mediates lipid oxidation | [128] |
| DPP4 | dipeptidyl peptidase 4 | Assists NOXs-mediated oxidation reaction | [129] | |
| NOXs | NADPH oxidases | Transfers electrons through the biofilm and reduces oxygen to superoxide, thus enabling the accumulation of ROS | [1] | |
| POR | NADPH-cytochrome P450 reductase | Promotes lipid peroxidation by Catalyzing the Production of H2O2 | [130] | |
| CyB5R1 | NADH-cytochrome b5 reductase | Promotes lipid peroxidation by Catalyzing the Production of H2O2 | [130] | |
| Iron metabolism | ELAVL1 | embryonic lethal, abnormal vision, Drosophila-like 1 | Selectively active ferrotinophagy as an RNA binding protein | [131] |
| ZFP36 | zinc-finger protein 36 | Selectively inactive ferrotinophagy as an RNA binding protein | [132] | |
| FTMT | mitochondrial ferritin | Stores free iron in mitochondria | [133] | |
| Prominin2 | Prominin2 | Mediates iron ion export by the exocytic form | [134] | |
| HO-1 | heme oxygenase-1 | Elevates intracellular free iron levels by promoting heme degradation | [135] | |
| SLC39A14 | solute carrier family 39 member 14 | Sensitizes cells to ferroptosis by mediating the transport of NTBI | [136] | |
| SLC11A2 | solute carrier family 11 member 2 | Sensitizes cells to ferroptosis by mediating the transport of NTBI | [136] | |
| SLC39A8 | solute carrier family 39 member 8 | Sensitizes cells to ferroptosis by mediating the transport of NTBI | [136] | |
| SLC40A1 | solute carrier family 40 member 1 | Sensitizes cells to ferroptosis by mediating the transport of NTBI | [136] | |
| Trf | transferrin | Extracellularly binds iron | [137] | |
| TfR | transferrin receptor | Mediates Transferrin bound iron import | [138] | |
| CISD1 | CDGSH iron sulfur domain 1 | Increases iron-mediated intramitochondrial lipid peroxidation | [139] | |
| HSPB1 | heat shock protein beta-1 | Inhibits of ferroptosis by affecting iron metabolism | [140] | |
| NFS1 | l-cysteine desulfurase | Inhibits ferroptosis by maintaining iron-sulfur cofactor stability | [141] | |
| Lipid metabolism | LPCAT3 | lysophosphatidyl-choline acyltransferase 3 | Involves in key steps of PUFA synthesis | [25,128] |
| ACSL4 | Long-chain acyl-CoA synthetase-4 | Mediates PUFA insertion into cell membranes | [118] | |
| AMPK | AMP-activated protein kinase | Energy stress-mediated regulation of PUFA synthesis | [142] | |
| ELOVL5 | elongation of very longchain fatty acid protein 5 | Affects the synthesis of PUFAs necessary for ferroptosis | [143] | |
| FADS1 | fatty acid desaturase 1 | Affects the synthesis of PUFAs necessary for ferroptosis | [143] | |
| PPARα | peroxisome proliferator-activated receptor α | Regulates intracellular lipid homeostasis | [144] | |
| ACSL3 | Long-chain acyl-CoA synthetase-3 | Mediates MUFA insertion into cell membranes | [124] | |
| SCD1 | Stearyl-coenzyme A desaturase 1 | Prevents ferroptosis by modulating ACSL4 activity | [123] | |
| RAB7A | member RAS oncogene family 7 | Regulates lipophagy | [145] | |
| Amino acid metabolism | SLC7A11 | solute carrier family 7 member 11 | Transports cysteine by composing the system xc- | [34] |
| SLC3A2 | solute carrier family 3 member 2 | Transports cysteine by composing the system xc- | [34] | |
| mTORC1 | mechanistic tar-get of rapamycin complex 1 | Promotes degradation of SLC7A11 in lysosomes | [146] | |
| mTORC2 | mechanistic target of rapamycin complex2 | Inhibits the activity of the SLC7A11 transporter by phosphorylating serine 26 of SLC7A11 | [147] | |
| CD44v | CD44 variant | Stabilizes system xc- activity | [148,149] | |
| GCLC | glutamylcysteine ligase | Involves in the synthesis of GSH, but also has unconventional anti-ferroptosis activity | [150,151] | |
| CBS | Corticobasal Syndrome | Participates in the rate-limiting step of the transsulfuration pathway | [152] | |
| CGL | coagulation | prevents cellular ferroptosis when cysteine acquisition is limited | [152] | |
| SLC38A1 | solute carrier family 38 member 1 | Mediates glutamate import and sensitizes ferroptosis | [153-155] | |
| SLC1A5 | solute carrier family 1 member 5 | Mediates glutamate import and sensitizes ferroptosis | [153-155] | |
| BECN1 | Beclin 1 | Directly binds to system xc - and blocks its activity | [156] | |
| GLS2 | glutaminase 2 | Prevents ferroptosis by mediating the degradation of glutamate | [153] | |
| Other metabolic pathways | ACSF2 | acyl-CoA synthetase family member 2 | Regulates mitochondria-associated lipid metabolism | [1] |
| VDAC2 | voltage-dependent Anion Channel2 | Iron transporter on mitochondria, affects iron availability | [157] | |
| FXN | Frataxin | Affects the availability of iron as well as some antioxidant enzyme activities by controlling the synthesis of iron-sulfur clusters | [158] | |
| NFE2L2 | nuclear factor erythroid synthase 2 | Affects ferroptosis by affecting the expression of a variety of ferroptosis-associated proteins | [159] | |
| TP53 | tumor protein 53 | Affects ferroptosis by affecting the expression of a variety of ferroptosis-associated proteins | [160] | |
| YAP | Yes-associated protein | Regulates lipid metabolism in the presence of high cell density | [68,161,162] |