Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts

Junfeng Ma, Partha Banerjee, Stephen A. Whelan, Ting Liu, An Chi Wei, Genaro Ramirez-Correa, Mark E. McComb, Catherine E. Costello, Brian O'Rourke, Anne M Murphy, Gerald Warren Hart

Research output: Contribution to journalArticle

Abstract

O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification on serine and threonine residues of many proteins, plays crucial regulatory roles in diverse biological events. As a nutrient sensor, O-GlcNAc modification (O-GlcNAcylation) on nuclear and cytoplasmic proteins underlies the pathology of diabetic complications including cardiomyopathy. However, mitochondrial O-GlcNAcylation, especially in response to chronic hyperglycemia in diabetes, has been poorly explored. We performed a comparative O-GlcNAc profiling of mitochondria from control and streptozotocin (STZ)-induced diabetic rat hearts by using an improved β-elimination/Michael addition with isotopic DTT reagents (BEMAD) followed by tandem mass spectrometric analysis. In total, 86 mitochondrial proteins, involved in diverse pathways, were O-GlcNAcylated. Among them, many proteins have site-specific alterations in O-GlcNAcylation in response to diabetes, which suggests that protein O-GlcNAcylation is a novel layer of regulation mediating adaptive changes in mitochondrial metabolism during the progression of diabetic cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)2254-2264
Number of pages11
JournalJournal of Proteome Research
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2016

Keywords

  • diabetic cardiomyopathy
  • mass spectrometry
  • mitochondria
  • O-GlcNAcome
  • O-GlcNAcylation
  • proteomics
  • pyruvate dehydrogenase

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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  • Cite this

    Ma, J., Banerjee, P., Whelan, S. A., Liu, T., Wei, A. C., Ramirez-Correa, G., McComb, M. E., Costello, C. E., O'Rourke, B., Murphy, A. M., & Hart, G. W. (2016). Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. Journal of Proteome Research, 15(7), 2254-2264. https://doi.org/10.1021/acs.jproteome.6b00250