The regulatory roles of O-GlcNAcylation in mitochondrial homeostasis and metabolic syndrome

Nutrients excess is one of the leading causes of metabolic syndrome globally. Protein post-translational O-GlcNAc modification has been recognized as an essential nutrient sensor of the cell. Emerging studies suggest that O-GlcNAcylation lies at the core linking nutritional stress to insulin resistance. Mitochondria are the major site for ATP production in most eukaryotes. Mitochondrial dysfunction and oxidative stress have long been considered as an important mechanism underlying insulin resistance. The metabolic process is under the influence of environmental and nutritional factors, thus sensing and transducing nutritional signals sit at the pivot of metabolism control. For a long time little was known about O-GlcNAcylation within mitochondria since mitochondrial O-GlcNAcylation was regarded rare. Recent findings have demonstrated that O-GlcNAcylation is widely spread among mitochondrial proteins, and that mitochondrial function and oxidative stress both can be regulated by O-GlcNAcylation, particularly under diabetic circumstances.