Ferroptosis signaling pathway

Schematic illustration of ferroptosis signaling pathway. Ferroptosis starts with Fe3+-bound transferrin (Tf) endocytosis via transferrin receptor 1 (TfR1). After endocytosis, Fe3+ is released from the Tf–TfR1 complex and is reduced to Fe2+ by endosomal metalloreductase, STEAP. Fe2+ can be transported and stored in ferritin by divalent metal transporter 1 (DMT1 or SLC11A2) or remain in the cytoplasm as a labile iron (Fe2+) pool (LIP). Fe2+-/Fe3+-catalyzed Fenton reaction generates the hydroxyl radical (OH•) that reacts with membrane lipids (the free polyunsaturated fatty acids or PUFA-OH) and produces lipid peroxidation product, PUFA-OOH. Lipid peroxidation can also occur via enzymes such as lipoxygenases (LOXs) such as 15-LOX-1 isoform and P450 oxidoreductase. Ferroptosis can be interdicted by iron chelators, antioxidants, and glutathione peroxidase 4 (GPX4) that converts PUFA-OOH back to PUFA-OH, using glutathione (GSH) as a substrate. GSH synthesis occurs via the entry of cystine into the cell by system Xc− [36]. Created with BioRender.com

Publication

A Concise Review on Oxidative Stress-Mediated Ferroptosis and Cuproptosis in Alzheimer’s Disease (2023) Xudong Huang, et al. Cells. 2023 May;12(10). Figure: F5. Homo sapiens

Disease mentions