Open Access Research article

Developmental stage-dependent metabolic regulation during meiotic differentiation in budding yeast

Thomas Walther123*, Fabien Létisse123, Lindsay Peyriga123, Ceren Alkim1, Yuchen Liu4, Aurélie Lardenois4, Hélène Martin-Yken123, Jean-Charles Portais123, Michael Primig4 and Jean Marie François123*

Author Affiliations

1 Université de Toulouse, INSA, UPS, INP, 135 Avenue de Rangueil, Toulouse, F-31077, France

2 INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, F-31400, France

3 CNRS, UMR5504, Toulouse, F-31400, France

4 Inserm U1085 IRSET, University of Rennes 1, Campus de Beaulieu, Rennes, 35042, France

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BMC Biology 2014, 12:60  doi:10.1186/s12915-014-0060-x

Published: 2 September 2014

Abstract

Background

The meiotic developmental pathway in yeast enables both differentiation of vegetative cells into haploid spores that ensure long-term survival, and recombination of the parental DNA to create genetic diversity. Despite the importance of proper metabolic regulation for the supply of building blocks and energy, little is known about the reprogramming of central metabolic pathways in meiotically differentiating cells during passage through successive developmental stages.

Results

Metabolic regulation during meiotic differentiation in budding yeast was analyzed by integrating information on genome-wide transcriptional activity, 26 enzymatic activities in the central metabolism, the dynamics of 67 metabolites, and a metabolic flux analysis at mid-stage meiosis. Analyses of mutants arresting sporulation at defined stages demonstrated that metabolic reprogramming is tightly controlled by the progression through the developmental pathway. The correlation between transcript levels and enzymatic activities in the central metabolism varies significantly in a developmental stage-dependent manner. The complete loss of phosphofructokinase activity at mid-stage meiosis enables a unique setup of the glycolytic pathway which facilitates carbon flux repartitioning into synthesis of spore wall precursors during the co-assimilation of glycogen and acetate. The need for correct homeostasis of purine nucleotides during the meiotic differentiation was demonstrated by the sporulation defect of the AMP deaminase mutant amd1, which exhibited hyper-accumulation of ATP accompanied by depletion of guanosine nucleotides.

Conclusions

Our systems-level analysis shows that reprogramming of the central metabolism during the meiotic differentiation is controlled at different hierarchical levels to meet the metabolic and energetic needs at successive developmental stages.

Keywords:
Differentiation; Flux analysis; Meiosis; Metabolic reprogramming; Metabolome; Systems biology; Transcriptome; Yeast