Glutathione Metabolism/Ferroptosis Antibody Sampler Kit #84600

Ferroptosis is an iron-dependent form of regulated cell death associated with increased 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. 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 (3). GPX4 converts reduced glutathione (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 xCT/SLC7A11 and SLC3A2/4F2hc/CD98, and is inhibited by the ferroptosis inducer erastin (4). Glutamate-cysteine ligase catalytic subunit (GCLC) catalyzes the ligation of glutamate and cysteine, the first and rate-limiting step in glutathione biosynthesis (5). SLC25A39 and its paralogue SLC25A40 were found to be essential for mitochondrial import of glutathione, providing protection against oxidative stress and mitochondrial dysfunction (6,7). Glutaminase catalyzes the conversion of glutamine to glutamate, the first and rate-limiting step of glutaminolysis (8). Both kidney-type glutaminase (GLS1) and liver-type glutaminase (GLS2) have been shown to act as tumor suppressors in some conditions (8). They have also been implicated in the regulation of ferroptosis (9,10). Glutamate oxaloacetate transaminase 1 and 2 (GOT1/GOT2) enzymes act downstream in glutamine metabolism in reactions producing aspartate. GOT1 catalyzes the cytoplasmic interconversion of aspartate and oxaloacetate (11). GOT1 inhibition promotes pancreatic cell death by ferroptosis (12). GOT2 catalyzes the conversion of oxaloacetate to aspartate in the mitochondria and has been shown to be an important regulator of cancer metabolism (13).