(G) A proposed model for a role of SIRT5 in mediating oxidative stress to increase IDH2 and G6PD activities, NADPH production, and cellular protection. SIRT5 is activated by oxidative stress by a yet unknown mechanism. The active SIRT5 stimulates IDH2 and G6PD by desuccinylation and deglutarylation, respectively, thereby increasing NADPH production and protecting cells from ROS damage. 