MPI für molekulare Genetik / Department of Vertebrate Genomics |
|Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress|
|Authors:||Ralser, Markus; Wamelink, Mirjam M.; Kowald, Axel; Gerisch, Birgit; Heeren, Gino; Struys, Eduard A.; Klipp, Edda; Jakobs, Cornelis; Breitenbach, Michael; Lehrach, H.; Krobitsch, Sylvia|
|Date of Publication (YYYY-MM-DD):||2007-12-21|
|Title of Journal:||Journal of Biology|
|Journal Abbrev.:||J Biol|
|Issue / Number:||4|
|Copyright:||© 1999-2008 BioMed Central Ltd|
|Review Status:||not specified|
|Abstract / Description:||Background
Eukaryotic cells have evolved various response mechanisms to counteract the deleterious consequences of oxidative stress. Among these processes, metabolic alterations seem to play an important role.
We recently discovered that yeast cells with reduced activity of the key glycolytic enzyme triosephosphate isomerase exhibit an increased resistance to the thiol-oxidizing reagent diamide. Here we show that this phenotype is conserved in Caenorhabditis elegans and that the underlying mechanism is based on a redirection of the metabolic flux from glycolysis to the pentose phosphate pathway, altering the redox equilibrium of the cytoplasmic NADP(H) pool. Remarkably, another key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is known to be inactivated in response to various oxidant treatments, and we show that this provokes a similar redirection of the metabolic flux.
The naturally occurring inactivation of GAPDH functions as a metabolic switch for rerouting the carbohydrate flux to counteract oxidative stress. As a consequence, altering the homoeostasis of cytoplasmic metabolites is a fundamental mechanism for balancing the redox state of eukaryotic cells under stress conditions.
|External Publication Status:||published|
|Communicated by:||Hans Lehrach|
|Affiliations:||MPI für molekulare Genetik|
|External Affiliations:||Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands;
Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria;
4Current address: Medical Proteome Center, Ruhr University Bochum, Universitätsstrasse 150, 44801 Bochum, Germany
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