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

作者：Gu Yuanyuan; Ande Sudharsana R; Mishra Suresh^*

来源：Archives of Biochemistry and Biophysics, 2011, 505(1): 98-104.

DOI：10.1016/j.abb.2010.09.024

• Hyperglycemia
• Mitochondrial dysfunction
• Insulin resistance
• Type 2 diabetes
• Tyrosine phosphorylation

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

• 出版日期2011-1-1