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• W3196298775 endingPage "2348" @default.
• W3196298775 startingPage "2348" @default.
• W3196298775 abstract "Acetylation is a post-translational modification that regulates the activity of enzymes fundamentally involved in cellular and mitochondrial bioenergetic metabolism. NAD+ dependent deacetylase sirtuin 3 (SIRT3) is localized to mitochondria where it plays a key role in regulating acetylation of TCA cycle enzymes and the mitochondrial respiratory complexes. Although the SIRT3 target proteins in mitochondria have been identified, the effect of SIRT3 activity on mitochondrial glucose metabolism in the brain remains elusive. The impact of abolished SIRT3 activity on glucose metabolism was determined in SIRT3 knockout (KO) and wild type (WT) mice injected with [1,6-13C]glucose using ex vivo 13C-NMR spectroscopy. The 1H-NMR spectra and amino acid analysis showed no differences in the concentration of lactate, glutamate, alanine, succinate, or aspartate between SIRT3 KO and WT mice. However, glutamine, total creatine (Cr), and GABA were lower in SIRT3 KO brain. Incorporation of label from [1,6-13C]glucose metabolism into lactate or alanine was not affected in SIRT3 KO brain. However, the incorporation of the label into all isotopomers of glutamate, glutamine, GABA and aspartate was lower in SIRT3 KO brain, reflecting decreased activity of mitochondrial and TCA cycle metabolism in both neurons and astrocytes. This is most likely due to hyperacetylation of mitochondrial enzymes due to suppressed SIRT3 activity in the brain of SIRT3 KO mice. Thus, the absence of Sirt3 results in impaired mitochondrial oxidative energy metabolism and neurotransmitter synthesis in the brain. Since the SIRT3 activity is NAD+ dependent, these results might parallel changes in glucose metabolism under pathologic reduction in mitochondrial NAD+ pools." @default.
• W3196298775 created "2021-09-13" @default.
• W3196298775 creator A5009419770 @default.
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• W3196298775 creator A5059402016 @default.
• W3196298775 date "2021-09-08" @default.
• W3196298775 modified "2023-10-18" @default.
• W3196298775 title "Perturbed Brain Glucose Metabolism Caused by Absent SIRT3 Activity" @default.
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• W3196298775 doi "https://doi.org/10.3390/cells10092348" @default.
• W3196298775 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8469836" @default.
• W3196298775 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34571997" @default.
• W3196298775 hasPublicationYear "2021" @default.
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