O-GlcNAcomic profiling identifies widespread O-linkedβ-N-acetylglucosamine modification (O-GlcNAcylation) in oxidative phosphorylation system regulating cardiac mitochondrial function

Junfeng Ma, Ting Liu, An Chi Wei, Partha Banerjee, Brian O'Rourke, Gerald W. Hart

Research output: Contribution to journalArticle

Abstract

Dynamic cycling of O-linkedβ-N-acetylglucosamine (OGlcNAc) on nucleocytoplasmic proteins serves as a nutrient sensor to regulate numerous biological processes. However, mitochondrial protein O-GlcNAcylation and its effects on function are largely unexplored. In this study, we performed a comparative analysis of the proteome and OGlcNAcome of cardiac mitochondria from rats acutely (12 h) treated without or with thiamet-G (TMG), a potent and specific inhibitor of O-GlcNAcase. We then determined the functional consequences in mitochondria isolated from the two groups. O-GlcNAcomic profiling finds that over 88 mitochondrial proteins are O-GlcNAcylated, with the oxidative phosphorylation system as a major target. Moreover, in comparison with controls, cardiac mitochondria from TMGtreated rats did not exhibit altered protein abundance but showed overall elevated O-GlcNAcylation of many proteins. However, O-GlcNAc was unexpectedly down-regulated at certain sites of specific proteins. Concomitantly, TMG treatment resulted in significantly increased mitochondrial oxygen consumption rates, ATP production rates, and enhanced threshold for permeability transition pore opening by Ca2+. Our data reveal widespread and dynamic mitochondrial proteinO-GlcNAcylation, serving as a regulator to their function.

Original languageEnglish (US)
Pages (from-to)29141-29153
Number of pages13
JournalJournal of Biological Chemistry
Volume290
Issue number49
DOIs
StatePublished - Dec 4 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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