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Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines

Cellular utilization of available energy flows to drive a multitude of forms of cellular “work” is a major biological constraint. Cells steer metabolism to address changing phenotypic states but little is known as to how bioenergetics couples to the richness of processes in a cell as a whole. Here,...

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Autores principales: Sevrin, Thomas, Strasser, Lisa, Ternet, Camille, Junk, Philipp, Caffarini, Miriam, Prins, Stella, D’Arcy, Cian, Catozzi, Simona, Oliviero, Giorgio, Wynne, Kieran, Kiel, Christina, Luthert, Philip J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874014/
https://www.ncbi.nlm.nih.gov/pubmed/36711246
http://dx.doi.org/10.1016/j.isci.2023.105931
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author Sevrin, Thomas
Strasser, Lisa
Ternet, Camille
Junk, Philipp
Caffarini, Miriam
Prins, Stella
D’Arcy, Cian
Catozzi, Simona
Oliviero, Giorgio
Wynne, Kieran
Kiel, Christina
Luthert, Philip J.
author_facet Sevrin, Thomas
Strasser, Lisa
Ternet, Camille
Junk, Philipp
Caffarini, Miriam
Prins, Stella
D’Arcy, Cian
Catozzi, Simona
Oliviero, Giorgio
Wynne, Kieran
Kiel, Christina
Luthert, Philip J.
author_sort Sevrin, Thomas
collection PubMed
description Cellular utilization of available energy flows to drive a multitude of forms of cellular “work” is a major biological constraint. Cells steer metabolism to address changing phenotypic states but little is known as to how bioenergetics couples to the richness of processes in a cell as a whole. Here, we outline a whole-cell energy framework that is informed by proteomic analysis and an energetics-based gene ontology. We separate analysis of metabolic supply and the capacity to generate high-energy phosphates from a representation of demand that is built on the relative abundance of ATPases and GTPases that deliver cellular work. We employed mouse embryonic fibroblast cell lines that express wild-type KRAS or oncogenic mutations and with distinct phenotypes. We observe shifts between energy-requiring processes. Calibrating against Seahorse analysis, we have created a whole-cell energy budget with apparent predictive power, for instance in relation to protein synthesis.
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spelling pubmed-98740142023-01-26 Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines Sevrin, Thomas Strasser, Lisa Ternet, Camille Junk, Philipp Caffarini, Miriam Prins, Stella D’Arcy, Cian Catozzi, Simona Oliviero, Giorgio Wynne, Kieran Kiel, Christina Luthert, Philip J. iScience Article Cellular utilization of available energy flows to drive a multitude of forms of cellular “work” is a major biological constraint. Cells steer metabolism to address changing phenotypic states but little is known as to how bioenergetics couples to the richness of processes in a cell as a whole. Here, we outline a whole-cell energy framework that is informed by proteomic analysis and an energetics-based gene ontology. We separate analysis of metabolic supply and the capacity to generate high-energy phosphates from a representation of demand that is built on the relative abundance of ATPases and GTPases that deliver cellular work. We employed mouse embryonic fibroblast cell lines that express wild-type KRAS or oncogenic mutations and with distinct phenotypes. We observe shifts between energy-requiring processes. Calibrating against Seahorse analysis, we have created a whole-cell energy budget with apparent predictive power, for instance in relation to protein synthesis. Elsevier 2023-01-05 /pmc/articles/PMC9874014/ /pubmed/36711246 http://dx.doi.org/10.1016/j.isci.2023.105931 Text en © 2023 The Authors. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sevrin, Thomas
Strasser, Lisa
Ternet, Camille
Junk, Philipp
Caffarini, Miriam
Prins, Stella
D’Arcy, Cian
Catozzi, Simona
Oliviero, Giorgio
Wynne, Kieran
Kiel, Christina
Luthert, Philip J.
Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines
title Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines
title_full Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines
title_fullStr Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines
title_full_unstemmed Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines
title_short Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines
title_sort whole-cell energy modeling reveals quantitative changes of predicted energy flows in ras mutant cancer cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874014/
https://www.ncbi.nlm.nih.gov/pubmed/36711246
http://dx.doi.org/10.1016/j.isci.2023.105931
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