Administration of exogenous NAD promotes Sirt5-mediated SDH-a desuccinylation by regulating the dynamic balance of succinylation, this desuccinylation process further reduces SDH-a activity, which in turn attenuates the succinate accumulation during ischemia and its depleting rate during reperfusion and finally alleviated O2·- generation [57]. The gene discussed is SDHA; the disease is ischemia.