Altered O-GlcNAc modification and phosphorylation of mitochondrial proteins in myoblast cells exposed to high glucose

Arch Biochem Biophys. 2011 Jan 1;505(1):98-104. doi: 10.1016/j.abb.2010.09.024. Epub 2010 Sep 29.

Abstract

Hyperglycemia induced increased posttranslational modification of proteins by O-linked-β-N-acetyl glucosamine (O-GlcNAcylation) and mitochondrial dysfunction has been independently implicated in the development of insulin resistance. It is not known whether repertoire of O-GlcNAcylated proteins includes mitochondrial proteins and their altered O-GlcNAcylation impinges on their phosphorylation mediated normal functioning thus contribute to mitochondrial dysfunction and insulin resistance. We have explored the O-GlcNAcylation of mitochondrial proteins from myoblast cells under basal (4mM) and high glucose (30mM) conditions using a combination of proteomic approaches. Furthermore, we have assessed the accompanied changes in the phosphorylation of mitochondrial proteins. We report that a number of mitochondrial proteins are O-GlcNAcylated under basal condition which is altered under high glucose condition. In addition, we report that exposure to high glucose not only changes the O-GlcNAcylation of mitochondrial proteins but also changes their phosphorylation profiles. The dynamic and complex interplay between O-GlcNAcylation and phosphorylation of mitochondrial proteins was further validated by immunoblot analysis of HSP60, prohibitin, and voltage-dependent anion channel 1 as candidate proteins. O-GlcNAcylation of mitochondrial proteins may play a role in normal functioning of mitochondria. High glucose induced changes in O-GlcNAcylation and phosphorylation of mitochondrial proteins may be associated with mitochondrial dysfunction and insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis
  • Cell Line
  • Cell Survival
  • Glucose / metabolism*
  • Hyperglycemia / metabolism*
  • Mice
  • Mitochondria / metabolism
  • Mitochondrial Proteins / metabolism*
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Mitochondrial Proteins
  • Adenosine Triphosphate
  • Proto-Oncogene Proteins c-akt
  • Glucose
  • Acetylglucosamine