Quantitative Analysis of Glycerol Accumulation, Glycolysis and Growth under Hyper Osmotic Stress
Journal article, 2013

We provide an integrated dynamic view on a eukaryotic osmolyte system, linking signaling with regulation of gene expression, metabolic control and growth. Adaptation to osmotic changes enables cells to adjust cellular activity and turgor pressure to an altered environment. The yeast Saccharomyces cerevisiae adapts to hyperosmotic stress by activating the HOG signaling cascade, which controls glycerol accumulation. The Hog1 kinase stimulates transcription of genes encoding enzymes required for glycerol production (Gpd1, Gpp2) and glycerol import (Stl1) and activates a regulatory enzyme in glycolysis (Pfk26/27). In addition, glycerol outflow is prevented by closure of the Fps1 glycerol facilitator. In order to better understand the contributions to glycerol accumulation of these different mechanisms and how redox and energy metabolism as well as biomass production are maintained under such conditions we collected an extensive dataset. Over a period of 180 min after hyperosmotic shock we monitored in wild type and different mutant cells the concentrations of key metabolites and proteins relevant for osmoadaptation. The dataset was used to parameterize an ODE model that reproduces the generated data very well. A detailed computational analysis using time-dependent response coefficients showed that Pfk26/27 contributes to rerouting glycolytic flux towards lower glycolysis. The transient growth arrest following hyperosmotic shock further adds to redirecting almost all glycolytic flux from biomass towards glycerol production. Osmoadaptation is robust to loss of individual adaptation pathways because of the existence and upregulation of alternative routes of glycerol accumulation. For instance, the Stl1 glycerol importer contributes to glycerol accumulation in a mutant with diminished glycerol production capacity. In addition, our observations suggest a role for trehalose accumulation in osmoadaptation and that Hog1 probably directly contributes to the regulation of the Fps1 glycerol facilitator. Taken together, we elucidated how different metabolic adaptation mechanisms cooperate and provide hypotheses for further experimental studies.

Author

Elzbieta Petelenz-Kurdziel

University of Gothenburg

C. Kuehn

Humboldt University of Berlin

Bodil Nordlander

University of Gothenburg

Dagmara Medrala Klein

University of Gothenburg

Kuk-ki Hong

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Therese Jacobson

University of Gothenburg

Peter Dahl

University of Gothenburg

J. Schaber

Humboldt University of Berlin

Otto von Guericke Universitaet Magdeburg

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Stefan Hohmann

University of Gothenburg

Edda Klipp

Humboldt University of Berlin

PLoS Computational Biology

1553-734X (ISSN) 1553-7358 (eISSN)

Vol. 9 6 artikel nr e1003084- e1003084

Subject Categories

Biochemistry and Molecular Biology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1371/journal.pcbi.1003084

More information

Latest update

9/6/2018 1