Open AccessPyruvate kinase variant of fission yeast tunes carbon metabolism, cell regulation, growth and stress resistance
Author(s) -
Kamrad Stephan,
Grossbach Jan,
RodríguezLópez Maria,
Mülleder Michael,
Townsend StJohn,
Cappelletti Valentina,
Stojanovski Gorjan,
CorreiaMelo Clara,
Picotti Paola,
Beyer Andreas,
Ralser Markus,
Bähler Jürg
Publication year - 2020
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20199270
Subject(s) - biology , yeast , pyruvate kinase , kinase , microbiology and biotechnology , metabolism , fission , saccharomyces cerevisiae , biochemistry , genetics , glycolysis , physics , quantum mechanics , neutron
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.