Cargando…
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,...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784877709602586624 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9874014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sevrinthomas wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT strasserlisa wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT ternetcamille wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT junkphilipp wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT caffarinimiriam wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT prinsstella wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT darcycian wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT catozzisimona wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT olivierogiorgio wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT wynnekieran wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT kielchristina wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines AT luthertphilipj wholecellenergymodelingrevealsquantitativechangesofpredictedenergyflowsinrasmutantcancercelllines |