O-GlcNAc modification is essential for the regulation of autophagy in Drosophila melanogaster

Cell Mol Life Sci. 2015 Aug;72(16):3173-83. doi: 10.1007/s00018-015-1889-z. Epub 2015 Apr 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Cell Line
  • DNA Primers / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / physiology*
  • Forkhead Transcription Factors / metabolism
  • Immunoblotting
  • Immunohistochemistry
  • Immunoprecipitation
  • Insulin / metabolism*
  • Microscopy, Electron, Transmission
  • N-Acetylglucosaminyltransferases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrans
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Starvation / metabolism*
  • Thiazoles

Substances

  • DNA Primers
  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Insulin
  • Pyrans
  • Thiazoles
  • thiamet G
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • Proto-Oncogene Proteins c-akt