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

Kamrad, S; Grossbach, J; Rodríguez-López, M; Mülleder, M; Townsend, S; Cappelletti, V; Stojanovski, G; ... Bähler, J; + view all (2020) Pyruvate kinase variant of fission yeast tunes carbon metabolism, cell regulation, growth and stress resistance. Molecular Systems Biology , 16 (4) , Article e9270. 10.15252/msb.20199270. Green open access

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Abstract

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 conserved region of Pyk1, the sole pyruvate kinase in fission yeast. 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 rebalancing triggered systems-level adjustments 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 does not lead to a growth advantage but to stress tolerance. The genetic tuning of glycolytic flux may reflect an adaptive trade-off in a species lacking pyruvate kinase isoforms.

Type: Article
Title: Pyruvate kinase variant of fission yeast tunes carbon metabolism, cell regulation, growth and stress resistance
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/msb.20199270
Publisher version: https://doi.org/10.15252/msb.20199270
Language: English
Additional information: © 2020 The Authors. Published under the terms of the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Keywords: cellular ageing, fermentation, glycolysis, oxidative stress, respiration
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10096806
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