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

Cellular physiology Protein

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
17 Feb 2023
Historique:
received: 08 06 2022
revised: 27 10 2022
accepted: 03 01 2023
entrez: 30 1 2023
pubmed: 31 1 2023
medline: 31 1 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36711246
doi: 10.1016/j.isci.2023.105931
pii: S2589-0042(23)00008-1
pmc: PMC9874014
doi:

Types de publication

Journal Article

Langues

eng

Pagination

105931

Informations de copyright

© 2023 The Authors.

Déclaration de conflit d'intérêts

The authors declare no competing interests.

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Auteurs

Thomas Sevrin (T)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Lisa Strasser (L)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Camille Ternet (C)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Philipp Junk (P)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Miriam Caffarini (M)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Stella Prins (S)

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.

Cian D'Arcy (C)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Simona Catozzi (S)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Giorgio Oliviero (G)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Kieran Wynne (K)

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin 4, Ireland.

Christina Kiel (C)

Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy.
Systems Biology Ireland, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.
UCD Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield Dublin 4, Ireland.

Philip J Luthert (PJ)

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
NIHR Moorfields Biomedical Research Centre, University College London, 11-43 Bath Street, London EC1V 9EL, UK.

Classifications MeSH