Sevrin, T; Strasser, L; Ternet, C; Junk, P; Caffarini, M; Prins, S; D'Arcy, C; ... Luthert, PJ; + view all Sevrin, T; Strasser, L; Ternet, C; Junk, P; Caffarini, M; Prins, S; D'Arcy, C; Catozzi, S; Oliviero, G; Wynne, K; Kiel, C; Luthert, PJ; - view fewer (2023) Whole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines. iScience , 26 (2) , Article 105931. 10.1016/j.isci.2023.105931.

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Abstract

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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