Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(1S,3R)-RSL3 | disrupts mitochondrial morphology and provokes strong mitochondrial impairment | Mus musculus | |
RSL3 | a selective GPx4 inhibitor, mediates concentration-dependent inhibition of GPX4, lipid peroxidation, enhanced mitochondrial fragmentation, loss of mitochondrial membrane potential, and reduced mitochondrial respiration. Ferroptosis inhibitors, such as deferoxamine, ferrostatin-1 and liproxstatin-1, but also CRISPR/Cas9 Bid knockout and the BID inhibitor BI-6c9 protect against RSL3 toxicity. Cell toxicity of the different RSL3 isomers in HT22 wild-type cells, overview | Mus musculus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrial membrane | - |
Mus musculus | 31966 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 glutathione + a hydroperoxy-fatty-acyl-[lipid] | Mus musculus | - |
glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | O70325 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Mus musculus | - |
fibroblast | mouse embryonic fibroblasts | Mus musculus | - |
HT-22 cell | - |
Mus musculus | - |
neuron | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 glutathione + a hydroperoxy-fatty-acyl-[lipid] | - |
Mus musculus | glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O | - |
? |
Synonyms | Comment | Organism |
---|---|---|
GPx4 | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | ferroptosis is an oxidative form of regulated necrotic cell death featuring glutathione (GSH) depletion, disrupted glutathione peroxidase-4 (GPX4) redox defense and detrimental lipid reactive oxygen species (ROS) formation. Mitochondrial damage in models of oxidative glutamate toxicity, glutathione peroxidase depletion, and ferroptosis. (1S,3R)-RSL3, a selective GPx4 inhibitor, mediates concentration-dependent inhibition of GPX4, lipid peroxidation, enhanced mitochondrial fragmentation, loss of mitochondrial membrane potential, and reduced mitochondrial respiration. Ferroptosis inhibitors, such as deferoxamine, ferrostatin-1 and liproxstatin-1, but also CRISPR/Cas9 Bid knockout and the BID inhibitor BI-6c9 protect against RSL3 toxicity. The mitochondria-targeted ROS scavenger mitoquinone (MitoQ) preserves mitochondrial integrity and function, and cell viability despite significant loss of GPX4 expression and associated increases in general lipid peroxidation after exposure to RSL3. BID inhibitor BI-6c9 and ferroptosis inhibitors abrogate 1S, 3R-RSL3 induced cell death, phenotypes, overview | Mus musculus |
metabolism | mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis | Mus musculus |