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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| Format: | Article |
| Language: | en_US |
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American Society for Cell Biology
2013
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| Online Access: | http://hdl.handle.net/1721.1/79047 https://orcid.org/0000-0003-2035-1820 |
| _version_ | 1826209052656402432 |
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| author | Botstein, David Slavov, Nikolai G |
| author2 | MIT Materials Research Laboratory |
| author_facet | MIT Materials Research Laboratory Botstein, David Slavov, Nikolai G |
| author_sort | Botstein, David |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T14:16:54Z |
| format | Article |
| id | mit-1721.1/79047 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:16:54Z |
| publishDate | 2013 |
| publisher | American Society for Cell Biology |
| record_format | dspace |
| spelling | mit-1721.1/790472022-10-01T20:19:10Z Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression Botstein, David Slavov, Nikolai G MIT Materials Research Laboratory Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Physics Slavov, Nikolai G. 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. National Institutes of Health (U.S.) (GM046406) National Institute of General Medical Sciences (U.S.) (Center for Quantitative Biology (GM071508) 2013-05-30T19:16:15Z 2013-05-30T19:16:15Z 2012-11 2012-10 Article http://purl.org/eprint/type/JournalArticle 1059-1524 1939-4586 http://hdl.handle.net/1721.1/79047 Slavov, N., and D. Botstein. Decoupling Nutrient Signaling from Growth Rate Causes Aerobic Glycolysis and Deregulation of Cell Size and Gene Expression. Molecular Biology of the Cell 24, no. 2 (January 10, 2013): 157-168. https://orcid.org/0000-0003-2035-1820 en_US http://dx.doi.org/10.1091/mbc.E12-09-0670 Molecular Biology of the Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Society for Cell Biology American Society for Cell Biology |
| spellingShingle | Botstein, David Slavov, Nikolai G 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 |
| url | http://hdl.handle.net/1721.1/79047 https://orcid.org/0000-0003-2035-1820 |
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