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ADP-dependent glucokinase regulates energy metabolism via ER-localized glucose sensing

Modulation of energy metabolism to a highly glycolytic phenotype, i.e. Warburg effect, is a common phenotype of cancer and activated immune cells allowing increased biomass-production for proliferation and cell division. Endoplasmic reticulum (ER)-localized ADP-dependent glucokinase (ADPGK) has been...

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Hauptverfasser: Imle, Roland (VerfasserIn) , Carl, Matthias (VerfasserIn) , Himmelreich, Nastassja (VerfasserIn) , Thiel, Christian (VerfasserIn) , Gröne, Hermann-Josef (VerfasserIn) , Poschet, Gernot (VerfasserIn) , Völkers, Mirko (VerfasserIn) , Gülow, Karsten (VerfasserIn) , Kölker, Stefan (VerfasserIn) , Sauer, Sven (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 03 October 2019
In: Scientific reports
Year: 2019, Jahrgang: 9
ISSN:2045-2322
DOI:10.1038/s41598-019-50566-6
Online-Zugang:Verlag, Volltext: https://doi.org/10.1038/s41598-019-50566-6
Verlag: https://www.nature.com/articles/s41598-019-50566-6
Volltext
Verfasserangaben:Roland Imle, Bei-Tzu Wang, Nicolas Stützenberger, Jana Birkenhagen, Amol Tandon, Matthias Carl, Nastassja Himmelreich, Christian Thiel, Hermann-Josef Gröne, Gernot Poschet, Mirko Völkers, Karsten Gülow, Anne Schröder, Sara Carillo, Stefan Mittermayr, Jonathan Bones, Marcin Mikołaj Kamiński, Stefan Kölker & Sven Wolfgang Sauer
Beschreibung
Zusammenfassung:Modulation of energy metabolism to a highly glycolytic phenotype, i.e. Warburg effect, is a common phenotype of cancer and activated immune cells allowing increased biomass-production for proliferation and cell division. Endoplasmic reticulum (ER)-localized ADP-dependent glucokinase (ADPGK) has been shown to play a critical role in T cell receptor activation-induced remodeling of energy metabolism, however the underlying mechanisms remain unclear. Therefore, we established and characterized in vitro and in vivo models for ADPGK-deficiency using Jurkat T cells and zebrafish. Upon activation, ADPGK knockout Jurkat T cells displayed increased cell death and ER stress. The increase in cell death resulted from a metabolic catastrophe and knockout cells displayed severely disturbed energy metabolism hindering induction of Warburg phenotype. ADPGK knockdown in zebrafish embryos led to short, dorsalized body axis induced by elevated apoptosis. ADPGK hypomorphic zebrafish further displayed dysfunctional glucose metabolism. In both model systems loss of ADPGK function led to defective N- and O-glycosylation. Overall, our data illustrate that ADPGK is part of a glucose sensing system in the ER modulating metabolism via regulation of N- and O-glycosylation.
Beschreibung:Gesehen am 25.10.2019
Beschreibung:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-019-50566-6

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