Determinants of brain cell metabolic phenotypes and energy substrate utilization unraveled with a modeling approach.

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ID Serval
serval:BIB_865BB600BF78
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Determinants of brain cell metabolic phenotypes and energy substrate utilization unraveled with a modeling approach.
Périodique
Plos Computational Biology
Auteur(s)
Neves A., Costalat R., Pellerin L.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
8
Numéro
9
Pages
e1002686
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Although all brain cells bear in principle a comparable potential in terms of energetics, in reality they exhibit different metabolic profiles. The specific biochemical characteristics explaining such disparities and their relative importance are largely unknown. Using a modeling approach, we show that modifying the kinetic parameters of pyruvate dehydrogenase and mitochondrial NADH shuttling within a realistic interval can yield a striking switch in lactate flux direction. In this context, cells having essentially an oxidative profile exhibit pronounced extracellular lactate uptake and consumption. However, they can be turned into cells with prominent aerobic glycolysis by selectively reducing the aforementioned parameters. In the case of primarily oxidative cells, we also examined the role of glycolysis and lactate transport in providing pyruvate to mitochondria in order to sustain oxidative phosphorylation. The results show that changes in lactate transport capacity and extracellular lactate concentration within the range described experimentally can sustain enhanced oxidative metabolism upon activation. Such a demonstration provides key elements to understand why certain brain cell types constitutively adopt a particular metabolic profile and how specific features can be altered under different physiological and pathological conditions in order to face evolving energy demands.
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/11/2012 18:28
Dernière modification de la notice
20/08/2019 14:45
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