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Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast

The regulatory roles of sphingolipids in diverse cell functions have been characterized extensively. However, the dynamics and interactions among the different sphingolipid species are difficult to assess, because de novo biosynthesis, metabolic inter-conversions, and the retrieval of sphingolipids...

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Autores principales: Chen, Po-Wei, Fonseca, Luis L., Hannun, Yusuf A., Voit, Eberhard O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667767/
https://www.ncbi.nlm.nih.gov/pubmed/23737740
http://dx.doi.org/10.1371/journal.pcbi.1003078
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author Chen, Po-Wei
Fonseca, Luis L.
Hannun, Yusuf A.
Voit, Eberhard O.
author_facet Chen, Po-Wei
Fonseca, Luis L.
Hannun, Yusuf A.
Voit, Eberhard O.
author_sort Chen, Po-Wei
collection PubMed
description The regulatory roles of sphingolipids in diverse cell functions have been characterized extensively. However, the dynamics and interactions among the different sphingolipid species are difficult to assess, because de novo biosynthesis, metabolic inter-conversions, and the retrieval of sphingolipids from membranes form a complex, highly regulated pathway system. Here we analyze the heat stress response of this system in the yeast Saccharomyces cerevisiae and demonstrate how the cell dynamically adjusts its enzyme profile so that it is appropriate for operation under stress conditions before changes in gene expression become effective. The analysis uses metabolic time series data, a complex mathematical model, and a custom-tailored optimization strategy. The results demonstrate that all enzyme activities rapidly increase in an immediate response to the elevated temperature. After just a few minutes, different functional clusters of enzymes follow distinct activity patterns. Interestingly, starting after about six minutes, both de novo biosynthesis and all exit routes from central sphingolipid metabolism become blocked, and the remaining metabolic activity consists entirely of an internal redistribution among different sphingoid base and ceramide pools. After about 30 minutes, heat stress is still in effect and the enzyme activity profile is still significantly changed. Importantly, however, the metabolites have regained concentrations that are essentially the same as those under optimal conditions.
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spelling pubmed-36677672013-06-04 Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast Chen, Po-Wei Fonseca, Luis L. Hannun, Yusuf A. Voit, Eberhard O. PLoS Comput Biol Research Article The regulatory roles of sphingolipids in diverse cell functions have been characterized extensively. However, the dynamics and interactions among the different sphingolipid species are difficult to assess, because de novo biosynthesis, metabolic inter-conversions, and the retrieval of sphingolipids from membranes form a complex, highly regulated pathway system. Here we analyze the heat stress response of this system in the yeast Saccharomyces cerevisiae and demonstrate how the cell dynamically adjusts its enzyme profile so that it is appropriate for operation under stress conditions before changes in gene expression become effective. The analysis uses metabolic time series data, a complex mathematical model, and a custom-tailored optimization strategy. The results demonstrate that all enzyme activities rapidly increase in an immediate response to the elevated temperature. After just a few minutes, different functional clusters of enzymes follow distinct activity patterns. Interestingly, starting after about six minutes, both de novo biosynthesis and all exit routes from central sphingolipid metabolism become blocked, and the remaining metabolic activity consists entirely of an internal redistribution among different sphingoid base and ceramide pools. After about 30 minutes, heat stress is still in effect and the enzyme activity profile is still significantly changed. Importantly, however, the metabolites have regained concentrations that are essentially the same as those under optimal conditions. Public Library of Science 2013-05-30 /pmc/articles/PMC3667767/ /pubmed/23737740 http://dx.doi.org/10.1371/journal.pcbi.1003078 Text en © 2013 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chen, Po-Wei
Fonseca, Luis L.
Hannun, Yusuf A.
Voit, Eberhard O.
Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast
title Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast
title_full Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast
title_fullStr Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast
title_full_unstemmed Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast
title_short Coordination of Rapid Sphingolipid Responses to Heat Stress in Yeast
title_sort coordination of rapid sphingolipid responses to heat stress in yeast
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667767/
https://www.ncbi.nlm.nih.gov/pubmed/23737740
http://dx.doi.org/10.1371/journal.pcbi.1003078
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