A working model illustrating regulation of the malate-aspartate shuttle by GOT2 acetylationShown is a working model depicting how acetylation of GOT2 at 3K regulates the malate-aspartate shuttle and promotes pancreatictumorproliferation. In pancreatictumorcells, reduced SIRT3 expression leads to an increase of GOT2 acetylation. GOT2 acetylation at 3K enhances the protein interaction between GOT2 and MDH2, thereby stimulating the net transfer of cytosolicNADH into mitochondria to support ATP production. Meanwhile, GOT2 3K acetylation promotes cellular NADPH production to suppress ROS that are produced during rapid cellproliferation. Glc, glucose; Gln, glutamine; Asp, aspartate; and Mal, malate. 