O-GlcNAcomic profiling identifies widespread O-GlcNAcylation in oxidative phosphorylation system regulating cardiac mitochondrial function
For our final Article of the Week of 2015, we feature a collaborative effort between Brian O’Rourke’s and Gerald Hart’s labs that was recently named one of the Journal of Biological Chemisty’s best of 2015. To see all of the 16 papers to receive this distinction, click here: http://www.jbc.org/content/290/49/29141.long
ARTICLE: O-GlcNAcomic profiling identifies widespread O-GlcNAcylation in oxidative phosphorylation system regulating cardiac mitochondrial function
AUTHORS: Ma J, Liu T, Wei AC, Banerjee P, O'Rourke B, Hart GW
JOURNAL: J Biol Chem. 2015 Dec 4;290(49):29141-53. doi: 10.1074/jbc.M115.691741. Epub 2015 Oct 7.
Dynamic cycling of O-linked β-N-acetylglucosamine (O-GlcNAc) 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 O-GlcNAcome 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 TMG-treated 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 Ca(2+). Our data reveal widespread and dynamic mitochondrial protein O-GlcNAcylation, serving as a regulator to their function.
For a link to the full article, click here: http://www.jbc.org/content/290/49/29141.long
Link to abstract online: http://www.ncbi.nlm.nih.gov/pubmed/?term=O-GlcNAcomic+profiling+identifies+widespread+O-GlcNAcylation+in+oxidative+phosphorylation+system+regulating+cardiac+mitochondrial+function