GLS2 is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. It plays an important role in the regulation of glutamine catabolism. It promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. It also increases cellular anti-oxidant function via NADH and glutathione production. GLS2 has been implicated in various cancers. It is overexpressed in triple-negative basal-like breast cancer (TNBC) and metastatic lung cancer, and it confers radioresistance in advanced human cervical cancer cells. GLS2 may also reduce reactive oxygen species (ROS) levels by increasing the level of cellular reduced glutathione (GSH), NADH, or NADPH, suggesting a role in cancer metabolism.
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