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:	Po-Wei Chen, Luis L Fonseca, Yusuf A Hannun, Eberhard O Voit
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7306700947e342d7b3902d79206e2cc5
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spelling	oai:doaj.org-article:7306700947e342d7b3902d79206e2cc52021-11-18T05:52:07ZCoordination of rapid sphingolipid responses to heat stress in yeast.1553-734X1553-735810.1371/journal.pcbi.1003078https://doaj.org/article/7306700947e342d7b3902d79206e2cc52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23737740/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The 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.Po-Wei ChenLuis L FonsecaYusuf A HannunEberhard O VoitPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 5, p e1003078 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Po-Wei Chen Luis L Fonseca Yusuf A Hannun Eberhard O Voit Coordination of rapid sphingolipid responses to heat stress in yeast.
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.
format	article
author	Po-Wei Chen Luis L Fonseca Yusuf A Hannun Eberhard O Voit
author_facet	Po-Wei Chen Luis L Fonseca Yusuf A Hannun Eberhard O Voit
author_sort	Po-Wei Chen
title	Coordination of rapid sphingolipid responses to heat stress in yeast.
title_short	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_sort	coordination of rapid sphingolipid responses to heat stress in yeast.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7306700947e342d7b3902d79206e2cc5
work_keys_str_mv	AT poweichen coordinationofrapidsphingolipidresponsestoheatstressinyeast AT luislfonseca coordinationofrapidsphingolipidresponsestoheatstressinyeast AT yusufahannun coordinationofrapidsphingolipidresponsestoheatstressinyeast AT eberhardovoit coordinationofrapidsphingolipidresponsestoheatstressinyeast
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Coordination of rapid sphingolipid responses to heat stress in yeast.

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