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Tytuł pozycji:

Redirected nuclear glutamate dehydrogenase supplies Tet3 with α-ketoglutarate in neurons.

Tytuł :
Redirected nuclear glutamate dehydrogenase supplies Tet3 with α-ketoglutarate in neurons.
Autorzy :
Traube FR; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Özdemir D; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Sahin H; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Scheel C; Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany.
Glück AF; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Geserich AS; Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany.
Oganesian S; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Kostidis S; Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, The Netherlands.
Iwan K; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Rahimoff R; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Giorgio G; Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany.
Müller M; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Spada F; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Biel M; Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany.
Cox J; Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany.
Giera M; Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, The Netherlands.
Michalakis S; Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany. .; Department of Ophthalmology, University Hospital, LMU Munich, Munich, Germany. .
Carell T; Department of Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany. .
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Źródło :
Nature communications [Nat Commun] 2021 Jul 02; Vol. 12 (1), pp. 4100. Date of Electronic Publication: 2021 Jul 02.
Typ publikacji :
Journal Article; Research Support, Non-U.S. Gov't
Język :
English
Imprint Name(s) :
Original Publication: [London] : Nature Pub. Group
MeSH Terms :
Cell Nucleus/*enzymology
Cell Nucleus/*metabolism
Dioxygenases/*metabolism
Glutamate Dehydrogenase/*metabolism
Ketoglutaric Acids/*metabolism
Neurons/*metabolism
Animals ; Brain/metabolism ; Citric Acid Cycle ; Dioxygenases/genetics ; Epigenomics ; Gene Expression ; Glutamate Dehydrogenase/genetics ; Glutamic Acid/metabolism ; HEK293 Cells ; Humans ; Ketoglutarate Dehydrogenase Complex/metabolism ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism ; Neuronal Plasticity
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Substance Nomenclature :
0 (Ketoglutaric Acids)
3KX376GY7L (Glutamic Acid)
EC 1.- (TET3 protein, human)
EC 1.13.11.- (Dioxygenases)
EC 1.13.11.- (Tet3 protein, mouse)
EC 1.2.4.2 (Ketoglutarate Dehydrogenase Complex)
EC 1.4.1.2 (Glutamate Dehydrogenase)
Entry Date(s) :
Date Created: 20210703 Date Completed: 20210722 Latest Revision: 20210722
Update Code :
20210914
PubMed Central ID :
PMC8253819
DOI :
10.1038/s41467-021-24353-9
PMID :
34215750
Czasopismo naukowe
Tet3 is the main α-ketoglutarate (αKG)-dependent dioxygenase in neurons that converts 5-methyl-dC into 5-hydroxymethyl-dC and further on to 5-formyl- and 5-carboxy-dC. Neurons possess high levels of 5-hydroxymethyl-dC that further increase during neural activity to establish transcriptional plasticity required for learning and memory functions. How αKG, which is mainly generated in mitochondria as an intermediate of the tricarboxylic acid cycle, is made available in the nucleus has remained an unresolved question in the connection between metabolism and epigenetics. We show that in neurons the mitochondrial enzyme glutamate dehydrogenase, which converts glutamate into αKG in an NAD + -dependent manner, is redirected to the nucleus by the αKG-consumer protein Tet3, suggesting on-site production of αKG. Further, glutamate dehydrogenase has a stimulatory effect on Tet3 demethylation activity in neurons, and neuronal activation increases the levels of αKG. Overall, the glutamate dehydrogenase-Tet3 interaction might have a role in epigenetic changes during neural plasticity.

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