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dc.contributor.authorKristian, Tibor
dc.contributor.authorKarimi, Arman J
dc.contributor.authorFearnow, Adam
dc.contributor.authorWaddell, Jaylyn
dc.contributor.authorMcKenna, Mary C
dc.date.accessioned2021-09-30T14:30:47Z
dc.date.available2021-09-30T14:30:47Z
dc.date.issued2021-09-08
dc.identifier.urihttp://hdl.handle.net/10713/16750
dc.description.abstractAcetylation 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.en_US
dc.description.urihttps://doi.org/10.3390/cells10092348en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCellsen_US
dc.subject13C-NMR spectroscopyen_US
dc.subjectNAD+en_US
dc.subjectSIRT3en_US
dc.subject[1,6-13C]glucoseen_US
dc.subjectacetylationen_US
dc.subjectknock out mouseen_US
dc.subjectmetabolismen_US
dc.subjectmitochondriaen_US
dc.titlePerturbed Brain Glucose Metabolism Caused by Absent SIRT3 Activityen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cells10092348
dc.identifier.pmid34571997
dc.source.volume10
dc.source.issue9
dc.source.countryUnited States
dc.source.countrySwitzerland


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