Pyruvate kinase variant of fission yeast tunes carbon metabolism, cell regulation, growth and stress resistance.
Stephan KamradJan GrossbachMaria Rodríguez-LópezMichael MüllederStJohn TownsendValentina CappellettiGorjan StojanovskiClara Correia-MeloPaola PicottiAndreas BeyerMarkus RalserJürg BählerPublished in: Molecular systems biology (2021)
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.
Keyphrases
- saccharomyces cerevisiae
- induced apoptosis
- genome wide
- oxidative stress
- cell cycle arrest
- single cell
- escherichia coli
- protein kinase
- endoplasmic reticulum stress
- gene expression
- dna damage
- type diabetes
- tyrosine kinase
- transcription factor
- copy number
- adipose tissue
- lactic acid
- blood pressure
- heat stress
- skeletal muscle
- metabolic syndrome
- cell therapy
- stress induced
- bone marrow
- insulin resistance
- pi k akt
- blood glucose
- atomic force microscopy
- single molecule
- weight loss