Open Access Highly Accessed Research article

Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress

Markus Ralser1*, Mirjam M Wamelink2, Axel Kowald14, Birgit Gerisch1, Gino Heeren3, Eduard A Struys2, Edda Klipp1, Cornelis Jakobs2, Michael Breitenbach3, Hans Lehrach1 and Sylvia Krobitsch1*

Author affiliations

1 Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany

2 Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands

3 Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria

4 Current address: Medical Proteome Center, Ruhr University Bochum, Universitätsstrasse 150, 44801 Bochum, Germany

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Citation and License

Journal of Biology 2007, 6:10  doi:10.1186/jbiol61

Published: 21 December 2007

Abstract

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.

Results

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.

Conclusion

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.