Fig. 5. A model depicting the role of differentially targeted OGT isoforms in glycan-dependent signaling. The studies described here suggest that transcription from the OGT gene and subsequent alternative splicing produces a number of isoforms including mOGT and ncOGT. The unique N-termini of these isoforms lead to segregation of mOGT into the mitochondrial membrane and targeting of ncOGT to the nucleus and cytoplasm. The hexosamine-signaling pathway is known to modulate the levels of UDP-GlcNAc in response to nutrients (glucose, glutamine, free fatty acids). The UDP-GlcNAc would then be used by each of the uniquely targeted OGT isoforms to modify different intracellular substrates. In the mitochondrion, mOGT may play a role in apoptosis and lipid and carbohydrate metabolism (see text). In the nucleus and cytosol, ncOGT is envisioned to mediate effects on translation, nuclear transport and transcriptional repression.