Dataset Information

Pyruvate kinase variant of fission yeast reprograms energy metabolism triggering systemic changes in cell regulation, growth and stress resistance

ABSTRACT: Cells balance glycolysis with respiration to support their energetic and biosynthetic needs in different environmental or physiological contexts. With abundant glucose, many cells prefer to grow by fermentation. Using 161 natural isolates of fission yeast, we investigated the genetic basis and phenotypic effects of the fermentation-respiration balance. The laboratory and a few other strains depended more on respiration. This trait was associated with a single-nucleotide polymorphism in a conserved region of Pyk1, the sole pyruvate kinase in fission yeast, while most organisms possess isoforms with different activity. This variant reduced Pyk1 activity and glycolytic flux. Replacing the ‘low-activity’ pyk1 allele in the laboratory strain with the ‘high-activity’ allele was sufficient to increase fermentation and decrease respiration. This metabolic reprogramming triggered systems-level adaptations in the transcriptome and proteome, and in cellular traits, including increased growth and chronological lifespan, but decreased resistance to oxidative stress. Thus, low Pyk1 activity provides no growth advantage but stress tolerance, despite increased respiration. The genetic tuning of glycolytic flux may reflect an adaptive trade-off in a species lacking pyruvate-kinase isoforms.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Schizosaccharomyces Pombe 972h-

SUBMITTER: Valentina Cappelletti

LAB HEAD: Picotti Paola

PROVIDER: PXD017833 | Pride | 2020-05-27

REPOSITORIES: Pride

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			Action	DRS
	20171026_25_VC_178_DDA_171101080256.msf	Msf
	20171026_25_VC_178_DDA_171101080256.raw	Raw
	20171026_25_VC_178_DIA_171105143059.raw	Raw
	20171026_26_VC_179_DDA_171101102357.msf	Msf
	20171026_26_VC_179_DDA_171101102357.raw	Raw

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Publications

Pyruvate kinase variant of fission yeast tunes carbon metabolism, cell regulation, growth and stress resistance.

Kamrad Stephan S Grossbach Jan J Rodríguez-López Maria M Mülleder Michael M Townsend StJohn S Cappelletti Valentina V Stojanovski Gorjan G Correia-Melo Clara C Picotti Paola P Beyer Andreas A Ralser Markus M Bähler Jürg J

Molecular systems biology 20200401 4

Cells balance glycolysis with respiration to support their metabolic needs in different environmental or physiological contexts. With abundant glucose, many cells prefer to grow by aerobic glycolysis or fermentation. Using 161 natural isolates of fission yeast, we investigated the genetic basis and phenotypic effects of the fermentation-respiration balance. The laboratory and a few other strains depended more on respiration. This trait was associated with a single nucleotide polymorphism in a co ...[more]

PMID: 32319721

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