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

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Serval ID
serval:BIB_865BB600BF78
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Determinants of brain cell metabolic phenotypes and energy substrate utilization unraveled with a modeling approach.
Journal
Plos Computational Biology
Author(s)
Neves A., Costalat R., Pellerin L.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
8
Number
9
Pages
e1002686
Language
english
Notes
Publication types: Journal Article
Abstract
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
Yes
Create date
08/11/2012 18:28
Last modification date
20/08/2019 14:45
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