GOT1, also known as cytoplasmic glutamic oxaloacetic transaminase, plays a critical role in multiple metabolic pathways crucial for cellular homeostasis. It participates in classical and non-classical glutamine metabolism, glycolytic metabolism, and other metabolic processes [2].

In pancreatic cancer, GOT1-driven pathways maintain redox balance. Inhibition of GOT1 reveals cysteine, glutathione, and lipid antioxidant function as metabolic vulnerabilities. Targeting these pathways triggers ferroptosis in GOT1 knockdown cells. Mechanistically, GOT1 inhibition represses mitochondrial metabolism, promotes a catabolic state, enhances labile iron availability through autophagy, and potentiates the activity of ferroptotic stimuli [1].

In T cells, genetic deletion of GOT1 promotes the generation of memory CD8+ T cells, while GOT1 enhances CD8+ T cell effector differentiation and function by maintaining intracellular redox balance and serine-mediated purine nucleotide biosynthesis [3].

In endothelial cells, the PGC-1α activator Medioresinol can prevent pyroptosis through the PPARα-GOT1 axis by promoting phenylalanine metabolism [4].

In conclusion, GOT1 is essential for maintaining normal metabolic and redox balance in cells. Its study through gene-knockout models has revealed its significance in cancer, especially pancreatic cancer, and in T-cell and endothelial-cell-related biological processes. These findings provide potential targets for cancer treatment and new insights into the regulation of immune and endothelial cell functions.