Ralser M~Lehrach H, 2008

Pubmed ID 19004802
Title A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth.
Authors Markus Ralser, Mirjam M Wamelink, Eduard A Struys, Christian Joppich, Sylvia Krobitsch, Cornelis Jakobs, Hans Lehrach
Abstract The glucose analogue 2-deoxy-D-glucose (2-DG) restrains growth of normal and malignant cells, prolongs the lifespan of C. elegans, and is widely used as a glycolytic inhibitor to study metabolic activity with regard to cancer, neurodegeneration, calorie restriction, and aging. Here, we report that separating glycolysis and the pentose phosphate pathway highly increases cellular tolerance to 2-DG. This finding indicates that 2-DG does not block cell growth solely by preventing glucose catabolism. In addition, 2-DG provoked similar concentration changes of sugar-phosphate intermediates in wild-type and 2-DG-resistant yeast strains and in human primary fibroblasts. Finally, a genome-wide analysis revealed 19 2-DG-resistant yeast knockouts of genes implicated in carbohydrate metabolism and mitochondrial homeostasis, as well as ribosome biogenesis, mRNA decay, transcriptional regulation, and cell cycle. Thus, processes beyond the metabolic block are essential for the biological properties of 2-DG.
Citation Proc. Natl. Acad. Sci. U.S.A. 2008; 105:17807-11


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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Ralser M~Lehrach H, 2008 growth (spot assay) 2-deoxy-D-glucose [0.20-0.25%] SC hap a 4,905 Discrete

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