Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect
Adaptation of metabolism is a response of many eukaryotic cells to nutrient heterogeneity in the cell microenvironment. One of these adaptations is the shift from respiratory to fermentative metabolism, also called the <i>Warburg/Crabtree effect</i>. It is a response to a very high nutri...
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doaj-4451f9acd70b4c97a5a7b04031e1e1292021-09-26T01:04:31ZengMDPI AGProcesses2227-97172021-08-0191496149610.3390/pr9091496Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree EffectLaetitia Gibart0Rajeev Khoodeeram1Gilles Bernot2Jean-Paul Comet3Jean-Yves Trosset4I3S, Laboratoire d’Informatique, Signaux et Systèmes de Sophia-Antipolis, 06900 Biot, FranceI3S, Laboratoire d’Informatique, Signaux et Systèmes de Sophia-Antipolis, 06900 Biot, FranceI3S, Laboratoire d’Informatique, Signaux et Systèmes de Sophia-Antipolis, 06900 Biot, FranceI3S, Laboratoire d’Informatique, Signaux et Systèmes de Sophia-Antipolis, 06900 Biot, FranceBio-Information Research Laboratory, Sup’Biotech, 94800 Villejuif, FranceAdaptation of metabolism is a response of many eukaryotic cells to nutrient heterogeneity in the cell microenvironment. One of these adaptations is the shift from respiratory to fermentative metabolism, also called the <i>Warburg/Crabtree effect</i>. It is a response to a very high nutrient increase in the cell microenvironment, even in the presence of oxygen. Understanding whether this metabolic transition <i>can result</i> from basic regulation signals between components of the central carbon metabolism are the the core question of this work. We use an extension of the René Thomas modeling framework for representing the regulations between the main catabolic and anabolic pathways of eukaryotic cells, and <i>formal methods</i> for confronting models with known biological properties in different microenvironments. The formal model of the regulation of eukaryote metabolism defined and validated here reveals the conditions under which this metabolic phenotype switch occurs. It clearly proves that currently known regulating signals within the main components of central carbon metabolism <i>can be sufficient</i> to bring out the Warburg/Crabtree effect. Moreover, this model offers a general perspective of the regulation of the central carbon metabolism that can be used to study other biological questions.https://www.mdpi.com/2227-9717/9/9/1496biological regulation networksregulation of cell metabolismsystems biologycentral carbon metabolismrespirationfermentation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laetitia Gibart Rajeev Khoodeeram Gilles Bernot Jean-Paul Comet Jean-Yves Trosset |
spellingShingle |
Laetitia Gibart Rajeev Khoodeeram Gilles Bernot Jean-Paul Comet Jean-Yves Trosset Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect Processes biological regulation networks regulation of cell metabolism systems biology central carbon metabolism respiration fermentation |
author_facet |
Laetitia Gibart Rajeev Khoodeeram Gilles Bernot Jean-Paul Comet Jean-Yves Trosset |
author_sort |
Laetitia Gibart |
title |
Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect |
title_short |
Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect |
title_full |
Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect |
title_fullStr |
Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect |
title_full_unstemmed |
Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect |
title_sort |
regulation of eukaryote metabolism: an abstract model explaining the warburg/crabtree effect |
publisher |
MDPI AG |
series |
Processes |
issn |
2227-9717 |
publishDate |
2021-08-01 |
description |
Adaptation of metabolism is a response of many eukaryotic cells to nutrient heterogeneity in the cell microenvironment. One of these adaptations is the shift from respiratory to fermentative metabolism, also called the <i>Warburg/Crabtree effect</i>. It is a response to a very high nutrient increase in the cell microenvironment, even in the presence of oxygen. Understanding whether this metabolic transition <i>can result</i> from basic regulation signals between components of the central carbon metabolism are the the core question of this work. We use an extension of the René Thomas modeling framework for representing the regulations between the main catabolic and anabolic pathways of eukaryotic cells, and <i>formal methods</i> for confronting models with known biological properties in different microenvironments. The formal model of the regulation of eukaryote metabolism defined and validated here reveals the conditions under which this metabolic phenotype switch occurs. It clearly proves that currently known regulating signals within the main components of central carbon metabolism <i>can be sufficient</i> to bring out the Warburg/Crabtree effect. Moreover, this model offers a general perspective of the regulation of the central carbon metabolism that can be used to study other biological questions. |
topic |
biological regulation networks regulation of cell metabolism systems biology central carbon metabolism respiration fermentation |
url |
https://www.mdpi.com/2227-9717/9/9/1496 |
work_keys_str_mv |
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