Fig. 1

O-GlcNAc-cycling enzymes. A Three OGT isoforms, two nucleocyplasmic (ncOGT and sOGT) and one mitochondrial (mOGT), are generated by alternative splicing of the OGT messenger RNA (MTS Mitochondria Targeting Sequence). OGT comprises a N-terminal domain containing tetra-tricopeptide repeats (TPR) involved in protein–protein interactions and a C-terminal domain with glycosyltransferase activity. The PPO domain (Phophosphatidylinositol Phosphate binding domain of OGT), located in the C-terminal part, is involved in the recruitment of the OGT to the plasma membrane, allowing its interaction with insulin signaling proteins. CD1, CD2 Catalytic domains 1 and 2. ID intervening domain. B Two OGA isoforms, long (L-OGA) and short (S-OGA) are generated by alternative splicing of the OGA messenger RNA. L-OGA comprises a hexosaminidase domain in its N-terminal region and a pseudo-histone acetyltransferase domain (HAT) in its C-terminal region. S-OGA does not have the pseudo-HAT domain and seems to be addressed to the mitochondria via a 15 specific amino acids sequence located in the C-terminal region. C O-GlcNAcylation is a highly dynamic process regulated by the different OGT and OGA isoforms in different cell compartments