TY - JOUR
T1 - O-GlcNAcomic profiling identifies widespread O-linkedβ-N-acetylglucosamine modification (O-GlcNAcylation) in oxidative phosphorylation system regulating cardiac mitochondrial function
AU - Ma, Junfeng
AU - Liu, Ting
AU - Wei, An Chi
AU - Banerjee, Partha
AU - O'Rourke, Brian
AU - Hart, Gerald W.
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/12/4
Y1 - 2015/12/4
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M115.691741
DO - 10.1074/jbc.M115.691741
M3 - Article
C2 - 26446791
AN - SCOPUS:84949008124
SN - 0021-9258
VL - 290
SP - 29141
EP - 29153
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 49
ER -