Nucleocytoplasmic human O-GlcNAc transferase is sufficient for O-GlcNAcylation of mitochondrial proteins

Riccardo Trapannone, Daniel Mariappa, Andrew T. Ferenbach, Daan M. F. van Aalten (Lead / Corresponding author)

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O-linked N-acetylglucosamine modification (O-GlcNAcylation) is a nutrient-dependent protein post-translational modification, dynamically and reversibly driven by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that catalyse the addition and the removal of the O-GlcNAc moieties to/from serine and threonine residues of target proteins, respectively. Increasing evidence suggests involvement of O-GlcNAcylation in many biological processes, including transcription, signalling, neuronal development and mitochondrial function. The presence of a mitochondrial O-GlcNAc proteome and a mitochondrial OGT isoform (mOGT) have been reported. We explored the presence of mOGT in human cell lines and mouse tissues. Surprisingly, analysis of genomic sequences indicates that this isoform cannot be expressed in most of the species analysed, except some primates. In addition, we were not able to detect endogenous mOGT in a range of human cell lines. Knock-down experiments and Western blot analysis of all the predicted OGT isoforms suggested the expression of only a single OGT isoform. In agreement with this, we demonstrate that overexpression of the nucleocytoplasmic OGT isoform (ncOGT) leads to increased O-GlcNAcylation of mitochondrial proteins, suggesting that ncOGT is necessary and sufficient for the generation of the O-GlcNAc mitochondrial proteome.
Original languageEnglish
Pages (from-to)1693-1702
Number of pages10
JournalBiochemical Journal
Issue number12
Early online date5 Apr 2016
Publication statusPublished - 10 Jun 2016


  • alternative splicing
  • glycobiology
  • mitochondria
  • O-GlcNAc transferase (OGT)
  • O-linked
  • N-acetylglucosamine (O-GlcNAc)
  • post-translational modification (PTM)


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