Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast

Abstract The diauxic shift in Saccharomyces cerevisiae is an ideal model to study how eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic operation. In this work, we generated time‐resolved physiological data, quantitative metabolome (69 intracellular metabolites) and proteom...

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Main Authors: Guillermo G Zampar, Anne Kümmel, Jennifer Ewald, Stefan Jol, Bastian Niebel, Paola Picotti, Ruedi Aebersold, Uwe Sauer, Nicola Zamboni, Matthias Heinemann
Format: Article
Language:English
Published: Springer Nature 2013-04-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2013.11
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author Guillermo G Zampar
Anne Kümmel
Jennifer Ewald
Stefan Jol
Bastian Niebel
Paola Picotti
Ruedi Aebersold
Uwe Sauer
Nicola Zamboni
Matthias Heinemann
author_facet Guillermo G Zampar
Anne Kümmel
Jennifer Ewald
Stefan Jol
Bastian Niebel
Paola Picotti
Ruedi Aebersold
Uwe Sauer
Nicola Zamboni
Matthias Heinemann
author_sort Guillermo G Zampar
collection DOAJ
description Abstract The diauxic shift in Saccharomyces cerevisiae is an ideal model to study how eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic operation. In this work, we generated time‐resolved physiological data, quantitative metabolome (69 intracellular metabolites) and proteome (72 enzymes) profiles. We found that the diauxic shift is accomplished by three key events that are temporally organized: (i) a reduction in the glycolytic flux and the production of storage compounds before glucose depletion, mediated by downregulation of phosphofructokinase and pyruvate kinase reactions; (ii) upon glucose exhaustion, the reversion of carbon flow through glycolysis and onset of the glyoxylate cycle operation triggered by an increased expression of the enzymes that catalyze the malate synthase and cytosolic citrate synthase reactions; and (iii) in the later stages of the adaptation, the shutting down of the pentose phosphate pathway with a change in NADPH regeneration. Moreover, we identified the transcription factors associated with the observed changes in protein abundances. Taken together, our results represent an important contribution toward a systems‐level understanding of how this adaptation is realized.
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spelling doaj.art-566f18f09ef34c4988f93c59c7a75b782024-11-03T12:55:54ZengSpringer NatureMolecular Systems Biology1744-42922013-04-019111310.1038/msb.2013.11Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeastGuillermo G Zampar0Anne Kümmel1Jennifer Ewald2Stefan Jol3Bastian Niebel4Paola Picotti5Ruedi Aebersold6Uwe Sauer7Nicola Zamboni8Matthias Heinemann9Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of GroningenETH Zurich, Institute of Molecular Systems BiologyETH Zurich, Institute of Molecular Systems BiologyETH Zurich, Institute of Molecular Systems BiologyMolecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of GroningenETH Zurich, Institute of Molecular Systems BiologyETH Zurich, Institute of Molecular Systems BiologyETH Zurich, Institute of Molecular Systems BiologyETH Zurich, Institute of Molecular Systems BiologyMolecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of GroningenAbstract The diauxic shift in Saccharomyces cerevisiae is an ideal model to study how eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic operation. In this work, we generated time‐resolved physiological data, quantitative metabolome (69 intracellular metabolites) and proteome (72 enzymes) profiles. We found that the diauxic shift is accomplished by three key events that are temporally organized: (i) a reduction in the glycolytic flux and the production of storage compounds before glucose depletion, mediated by downregulation of phosphofructokinase and pyruvate kinase reactions; (ii) upon glucose exhaustion, the reversion of carbon flow through glycolysis and onset of the glyoxylate cycle operation triggered by an increased expression of the enzymes that catalyze the malate synthase and cytosolic citrate synthase reactions; and (iii) in the later stages of the adaptation, the shutting down of the pentose phosphate pathway with a change in NADPH regeneration. Moreover, we identified the transcription factors associated with the observed changes in protein abundances. Taken together, our results represent an important contribution toward a systems‐level understanding of how this adaptation is realized.https://doi.org/10.1038/msb.2013.11diauxic shiftfluxomemetabolomeproteomeSaccharomyces cerevisiae
spellingShingle Guillermo G Zampar
Anne Kümmel
Jennifer Ewald
Stefan Jol
Bastian Niebel
Paola Picotti
Ruedi Aebersold
Uwe Sauer
Nicola Zamboni
Matthias Heinemann
Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast
Molecular Systems Biology
diauxic shift
fluxome
metabolome
proteome
Saccharomyces cerevisiae
title Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast
title_full Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast
title_fullStr Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast
title_full_unstemmed Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast
title_short Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast
title_sort temporal system level organization of the switch from glycolytic to gluconeogenic operation in yeast
topic diauxic shift
fluxome
metabolome
proteome
Saccharomyces cerevisiae
url https://doi.org/10.1038/msb.2013.11
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