Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose

Authors:

Johan H. van Heerden1,3,4, Meike T. Wortel1,3,4, Frank J. Bruggeman1,4, Joseph J. Heijnen2,3, Yves J.M. Bollen4,5, Robert Planqué6, Josephus Hulshof6, Tom G. O’Toole7, S. Aljoscha Wahl2,3 and Bas Teusink1,3,4

doi: 10.15698/mic2014.01.133
Volume 1, pp. 103 to 106, published 20/02/2014.

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Affiliations:

1 Systems Bioinformatics/AIMMS/NISB, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.

2 Department of Biotechnology, Delft University of Technology, Julianalaan 67, Delft 2628 BC, Netherlands.

3 Kluyver Centre for Genomics of Industrial Fermentation/NCSB, Delft University of Technology, Julianalaan 67, Delft 2628 BC, The Netherlands.

4 Department of Molecular Cell Biology, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.

5 LaserLaB Amsterdam, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.

6 Department of Mathematics, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.

7 Department of Molecular Cell Biology and Immunology, Vrije University Medical Center, v/d Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.

Keywords: 

carbon metabolism, glycolysis, dynamic regulation, metabolic model, bistability, heterogeneity, yeast.

Corresponding Author(s):

Bas Teusink, De Boelelaan 1085; 1081HV Amsterdam, The Netherlands b.teusink@vu.nl

Conflict of interest statement:

The authors declare no competing financial interests.

Please cite this article as:

Johan H. van Heerden, Meike T. Wortel, Frank J. Bruggeman, Joseph J. Heijnen, Yves J.M. Bollen, Robert Planqué, Josephus Hulshof, Tom G. O’Toole, S. Aljoscha Wahl and Bas Teusink (2014) Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose. Microbial Cell 1(3): 103-106.

© van Heerden et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

In the model eukaryote Saccharomyces cerevisiae, it has long been known that a functional trehalose pathway is indispensable for transitions to high glucose conditions. Upon addition of glucose, cells with a defect in trehalose 6-phosphate synthase (Tps1), the first committed step in the trehalose pathway, display what we have termed an imbalanced glycolytic state; in this state the flux through the upper part of glycolysis outpaces that through the lower part of glycolysis. As a consequence, the intermediate fructose 1,6-bisphosphate (FBP) accumulates at low concentrations of ATP and inorganic phosphate (Pi). Despite significant research efforts, a satisfactory understanding of the regulatory role that trehalose metabolism plays during such transitions has remained infamously unresolved. In a recent study, we demonstrate that the startup of glycolysis exhibits two dynamic fates: a proper, functional, steady state or the imbalanced state described above. Both states are stable, attracting states, and the probability distribution of initial states determines the fate of a yeast cell exposed to glucose. Trehalose metabolism steers the dynamics of glycolysis towards the proper functional state through its ATP hydrolysis activity; a mechanism that ensures that the demand and supply of ATP is balanced with Pi availability under dynamic conditions. [van Heerden et al. Science (2014), DOI: 10.1126/science.1245114.]