Intestinal epithelial cell ferroptosis

Intestinal epithelial cell (IEC) ferroptosis is a specialized form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels [Dixon et al., 2012, Cell]. In the gastrointestinal tract, this process is primarily governed by the activity of glutathione peroxidase 4 (GPX4), which neutralizes lipid peroxides using glutathione as a essential cofactor. Dysregulation of this pathway is a critical driver of intestinal barrier dysfunction and mucosal inflammation, particularly in inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease [Xu et al., 2021, Nature Communications]. While inhibiting ferroptosis offers a therapeutic avenue for treating inflammatory conditions and ischemia-reperfusion injury, inducing this pathway is a strategy being explored to overcome apoptosis resistance in colorectal cancer cells [Sui et al., 2018, Cancer Letters]. Pharmacological intervention typically involves the use of small-molecule inhibitors like ferrostatin-1 or iron chelators to mitigate tissue damage, or the use of inducers like erastin to target malignant growth.

Other names

IEC ferroptosisFerroptotic cell death of the intestinal epitheliumIron-dependent intestinal epithelial cell death

Ferroptosis is regulated through the inhibition of lipid peroxide accumulation via the GPX4/GSH axis or the sequestration of labile iron [Dixon et al., 2012, Cell]. Pharmacological agents like Ferrostatin-1 act as radical-trapping antioxidants to prevent the oxidative destruction of membrane lipids, while iron chelators like Deferoxamine reduce the availability of iron required for the Fenton reaction [Conrad et al., 2018, Nature Chemical Biology].