Ferroptosis Antibody Sampler Kit #29650

Ferroptosis is an iron-dependent form of regulated cell death associated with an increase in lipid peroxides (reviewed in 1,2). Free divalent iron (Fe²⁺) can lead to spontaneous lipid peroxidation through a Fenton reaction. Ferroptosis is regulated by signaling pathways that control iron storage and oxidative stress. Iron homeostasis is controlled, in part, by ferritin, an iron storage protein consisting of a complex of heavy (FTH1) and light (FTL) chains. Levels of ferritin may be regulated by a selective autophagy process targeting ferritin, termed ferritinophagy. This pathway is mediated by nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor for ferritin (3,4). The divalent metal transporter SLC11A2/DMT1/NRAMP2 regulates iron homeostasis through non-heme absorption in the intestine (5). The glutathione peroxidase pathway has been identified as a key antioxidant defense pathway triggering ferroptosis. The compound RSL3, which directly inhibits GPX4, was identified as an activator of ferroptosis (6). GPX4 converts GSH into oxidized glutathione (GSSH) and reduces cytotoxic lipid peroxides. The glutathione peroxidase pathway is further regulated by System Xc-, an amino acid antiporter consisting of a disulfide-linked heterodimer of SLC7A11/xCT and SLC3A2/4F2hc/CD98, and is inhibited by the ferroptosis inducer erastin (7). Regulation of genes involved in oxidative stress, including GPX4, are largely controlled by the transcription factor NRF2 and serves as a defense against ferroptosis (8). Under normal conditions, expression of NRF2 is inhibited through interaction with KEAP1, part of a ubiquitin E3 ligase complex that leads to NRF2 proteasomal degradation. Oxidative stress leads to conformational changes in KEAP1 that disrupts this interaction, resulting in stabilization of NRF2. This process is further regulated through the autophagy pathway in which the autophagy cargo receptor p62/SQSTM1 can competitively inhibit the KEAP1-NRF2 complex, leading to upregulation of NRF2.