Signaling pathways involved in ferroptosis

Signaling pathways involved in ferroptosis. After entering, cystine via system XC− antiporter GPX4 works as an antioxidant and reduces intracellular ROS. However, HSPA5 enhances GPX4 antioxidant activity by stabilizing this enzyme. HSP90 inhibits this antioxidant and subsequently increases ROS. On the one hand, ER enhances GPX4 via AFT4, facilitating HSPA5 expression. On the other hand, it facilitates PLOOH by releasing ACSL4. Mitochondria increases ROS levels via different cycles, including the Fenton reaction and TCA. Iron accumulation, the product of ferritinophagy or degradation of SLC40A1, provides an ingredient for the Fenton reaction. Ferritinophagy is also enhanced by autophagy receptors, NCO4, or SQSTM1. Lipid peroxidation results in ferroptosis and pore formation, which NUPR1 can inhibit. Abbreviations: SLC32A, Solute Carrier Family 32; ASLC7A11, Solute Carrier Family 7A11; AFT4, Adaptive Fourier Transform 4; GSH, glutathione; GSSG, oxidized glutathione; GPX4, glutathione peroxidase 4; HSP90, Heat Shock Protein 90; HSP5A, Heat Shock Protein 5A; ROS, Reactive Oxygen Species; NUPR1, Nuclear Protein 1; ACSL4, Acyl-CoA Synthetase Long-Chain Family Member 4; ACACA, Acetyl-CoA Carboxylase Alpha; FA, fatty acid; FASN, fatty acid synthase; PUFA, Polyunsaturated Fatty Acid; ALOX, Arachidonate Lipoxygenase; PLOOH, phospholipid hydroperoxide; NCO4, nuclear coactivator 4; SQSTM1, sequestosome 1. Created with BioRender.com. Accessed on 30 July 2023.

Publication

Genome, Metabolism, or Immunity: Which Is the Primary Decider of Pancreatic Cancer Fate through Non-Apoptotic Cell Death? (2023) Erfaneh Barar, et al. Biomedicines. 2023 Oct;11(10). Figure: F1. Homo sapiens

Disease mentions