Glutaminase C Induces Oxidative Stress via Its Enzymatic Activity
This study clarifies the key role of Glutaminase C (GAC) in inducing oxidative stress dependent on its enzymatic activity. Neuronal cells overexpressing GAC (GAC-OE) and those overexpressing an enzymatic activity site mutant of GAC (GAC(K507E)) were generated and analyzed by transcriptomics. In HT-22, GAC-OE, and GAC(K507E) cells, upregulation of GAC enzymatic activity significantly increased ROS levels, whereas loss-of-function mutation of enzymatic activity completely abolished this effect. This finding reveals an independent function of GAC beyond its metabolic pathway and provides a theoretical basis for targeting GAC enzymatic activity in the treatment of Alzheimer's disease.