The Role Of IDH2 SUMOylation In Oxidative Stress

SUMO(Small ubiquitin-like Modifier)modification is a reversible post-translational modification of proteins,it plays a regulatory role on a large number of proteins located in the nucleus and cytoplasm,but the regulatory role of SUMOylation in mitochondria has been poorly studied.Isocitrate Dehydrogenase 2(IDH2)locates in mitochondria and catalyzes the conversion of Isocitrate to α-ketoglutarate(α-KG)in the tricarboxylic acid cycle,while generating reduced nicotinamide adenine dinucleotide phosphate(NADPH),which can maintain the rate of GSH/GSSG(Reduced and oxidized glutathione hormone)in mitochondria.IDH2 enzyme activity is regulated by acetylation and succinylation,both of which inhibit IDH2 enzyme activity.Whether SUMOylation can regulate IDH2 enzyme activity has not been reported.In this paper,we found that IDH2 can modified by SUMO1,conjugated with SUMO1 can increase the enzyme activity of IDH2 and further increase the production of NADPH and GSH/GSSG in mitochondria.Under oxidative stress,the SUMOylation of IDH2 contributes to the maintenance of cell morphology,the increase of cell viability and the reduction of apoptosis.The mechanism is that oxidative stress enhances the SUMOylation of IDH2,which may be mediated by the decrease of SENP1 enzyme activity.Therefore,SUMO1 modification of IDH2 is a protective regulation of cells in oxidative stress.