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Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression

To survive and proliferate, cells need to coordinate their metabolism, gene expression, and cell division. To understand this coordination and the consequences of its failure, we uncoupled biomass synthesis from nutrient signaling by growing, in chemostats, yeast auxotrophs for histidine, lysine, or...

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Autores principales: Slavov, Nikolai, Botstein, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541962/
https://www.ncbi.nlm.nih.gov/pubmed/23135997
http://dx.doi.org/10.1091/mbc.E12-09-0670
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author Slavov, Nikolai
Botstein, David
author_facet Slavov, Nikolai
Botstein, David
author_sort Slavov, Nikolai
collection PubMed
description To survive and proliferate, cells need to coordinate their metabolism, gene expression, and cell division. To understand this coordination and the consequences of its failure, we uncoupled biomass synthesis from nutrient signaling by growing, in chemostats, yeast auxotrophs for histidine, lysine, or uracil in excess of natural nutrients (i.e., sources of carbon, nitrogen, sulfur, and phosphorus), such that their growth rates (GRs) were regulated by the availability of their auxotrophic requirements. The physiological and transcriptional responses to GR changes of these cultures differed markedly from the respective responses of prototrophs whose growth-rate is regulated by the availability of natural nutrients. The data for all auxotrophs at all GRs recapitulated the features of aerobic glycolysis, fermentation despite high oxygen levels in the growth media. In addition, we discovered wide bimodal distributions of cell sizes, indicating a decoupling between the cell division cycle (CDC) and biomass production. The aerobic glycolysis was reflected in a general signature of anaerobic growth, including substantial reduction in the expression levels of mitochondrial and tricarboxylic acid genes. We also found that the magnitude of the transcriptional growth-rate response (GRR) in the auxotrophs is only 40–50% of the magnitude in prototrophs. Furthermore, the auxotrophic cultures express autophagy genes at substantially lower levels, which likely contributes to their lower viability. Our observations suggest that a GR signal, which is a function of the abundance of essential natural nutrients, regulates fermentation/respiration, the GRR, and the CDC.
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spelling pubmed-35419622013-03-30 Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression Slavov, Nikolai Botstein, David Mol Biol Cell Articles To survive and proliferate, cells need to coordinate their metabolism, gene expression, and cell division. To understand this coordination and the consequences of its failure, we uncoupled biomass synthesis from nutrient signaling by growing, in chemostats, yeast auxotrophs for histidine, lysine, or uracil in excess of natural nutrients (i.e., sources of carbon, nitrogen, sulfur, and phosphorus), such that their growth rates (GRs) were regulated by the availability of their auxotrophic requirements. The physiological and transcriptional responses to GR changes of these cultures differed markedly from the respective responses of prototrophs whose growth-rate is regulated by the availability of natural nutrients. The data for all auxotrophs at all GRs recapitulated the features of aerobic glycolysis, fermentation despite high oxygen levels in the growth media. In addition, we discovered wide bimodal distributions of cell sizes, indicating a decoupling between the cell division cycle (CDC) and biomass production. The aerobic glycolysis was reflected in a general signature of anaerobic growth, including substantial reduction in the expression levels of mitochondrial and tricarboxylic acid genes. We also found that the magnitude of the transcriptional growth-rate response (GRR) in the auxotrophs is only 40–50% of the magnitude in prototrophs. Furthermore, the auxotrophic cultures express autophagy genes at substantially lower levels, which likely contributes to their lower viability. Our observations suggest that a GR signal, which is a function of the abundance of essential natural nutrients, regulates fermentation/respiration, the GRR, and the CDC. The American Society for Cell Biology 2013-01-15 /pmc/articles/PMC3541962/ /pubmed/23135997 http://dx.doi.org/10.1091/mbc.E12-09-0670 Text en © 2013 Slavov and Botstein. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Slavov, Nikolai
Botstein, David
Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression
title Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression
title_full Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression
title_fullStr Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression
title_full_unstemmed Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression
title_short Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression
title_sort decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541962/
https://www.ncbi.nlm.nih.gov/pubmed/23135997
http://dx.doi.org/10.1091/mbc.E12-09-0670
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