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

Fingerprint

Proteomics
Medical problems
Diabetic Cardiomyopathies
Proteins
Acetylglucosamine
Mitochondrial Proteins
Diabetes Complications
Threonine
Post Translational Protein Processing
Streptozocin
Nuclear Proteins
Cardiomyopathies
Hyperglycemia
Serine
Mitochondria
Pathology
Metabolism
Nutrients
Rats
Food

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. / Ma, Junfeng; Banerjee, Partha; Whelan, Stephen A.; Liu, Ting; Wei, An Chi; Ramirez-Correa, Genaro; McComb, Mark E.; Costello, Catherine E.; O'Rourke, Brian; Murphy, Anne M; Hart, Gerald Warren.

In: Journal of Proteome Research, Vol. 15, No. 7, 01.07.2016, p. 2254-2264.

Research output: Contribution to journalArticle

Ma, Junfeng ; Banerjee, Partha ; Whelan, Stephen A. ; Liu, Ting ; Wei, An Chi ; Ramirez-Correa, Genaro ; McComb, Mark E. ; Costello, Catherine E. ; O'Rourke, Brian ; Murphy, Anne M ; Hart, Gerald Warren. / Comparative Proteomics Reveals Dysregulated Mitochondrial O-GlcNAcylation in Diabetic Hearts. In: Journal of Proteome Research. 2016 ; Vol. 15, No. 7. pp. 2254-2264.
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