O-GlcNAcylation is a dynamic post-translational modification that takes place on ser/thr residues of nucleocytoplasmic proteins. O-GlcNAcylation regulates almost all cellular events as a nutrient sensor, a transcriptional and translational regulator, and a disease-related factor. Although the role of O-GlcNAcylation in insulin signaling and metabolism are well established, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we manipulated O-GlcNAcylation in Drosophila and found that it regulates autophagy through Akt/dFOXO signaling. We demonstrate that O-GlcNAcylation and the levels of O-GlcNAc transferase (OGT) are increased during starvation. Furthermore, Atg proteins and autolysosomes are increased in OGT-reduced flies without fasting. Atg proteins and autophagosomes are reduced in OGT-overexpressing flies. Our results suggest that not only autophagy gene expression but also autophagic structures are regulated by OGT through Akt and dFOXO. These data imply that O-GlcNAcylation is important in modulating autophagy as well as insulin signaling in Drosophila.
Bibliographical noteFunding Information:
We thank K. M. Choe, and K. Yu for fly stocks and DNA clones, and O. Puig and K. Yu for providing the anti dFOXO antibody. We are also grateful to other members of the Cho and Choe laboratories for helpful discussions. This work is partly supported by the Graduate School of Yonsei University. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2013R1A2A1A01008067) to J. W. C.
© 2015 Springer Basel.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology