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A catabolic block does not sufficiently explain how 2-deoxy-d-glucose inhibits cell growth

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50483

Ralser,  Markus
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

Joppich,  Christian
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50396

Krobitsch,  Sylvia
Neurodegenerative Disorders (Sylvia Krobitsch), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50409

Lehrach,  Hans
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Ralser, M., Wamelink, M. M., Struys, E. A., Joppich, C., Krobitsch, S., Jakobs, C., et al. (2008). A catabolic block does not sufficiently explain how 2-deoxy-d-glucose inhibits cell growth. Proceedings of the National Academy of Sciences of the United States of America (Washington, DC), 105(46), 17807-17811. doi:10.1073/pnas.0803090105.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-7EAE-7
Zusammenfassung
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.