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Mol Cell. 2015 Aug 6;59(3):491-501. doi: 10.1016/j.molcel.2015.06.035.

Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect.

Author information

1
Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland; Institut de Génomique Fonctionnelle Labex ICST; INSERM U661, CNRS UMR5203; Université Montpellier, 141, rue de la Cardonille, 34094 Montpellier cedex 5, France.
2
Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland.
3
ETH Zurich, Institute of Molecular Systems Biology Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland.
4
Institute for Research on Cancer and Aging of Nice (IRCAN), University of Nice Sophia Antipolis, Centre A. Lacassagne, 06189 Nice, France.
5
Institute for Research on Cancer and Aging of Nice (IRCAN), University of Nice Sophia Antipolis, Centre A. Lacassagne, 06189 Nice, France; Centre Scientifique de Monaco, 8, Quai Antoine 1er MC, 98000, Monaco.
6
Department of Cell Biology, University of Geneva, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland. Electronic address: jean-claude.martinou@unige.ch.

Abstract

The transport of pyruvate into mitochondria requires a specific carrier, the mitochondrial pyruvate carrier (MPC). The MPC represents a central node of carbon metabolism, and its activity is likely to play a key role in bioenergetics. Until now, investigation of the MPC activity has been limited. However, the recent molecular identification of the components of the carrier has allowed us to engineer a genetically encoded biosensor and to monitor the activity of the MPC in real time in a cell population or in a single cell. We report that the MPC activity is low in cancer cells, which mainly rely on glycolysis to generate ATP, a characteristic known as the Warburg effect. We show that this low activity can be reversed by increasing the concentration of cytosolic pyruvate, thus increasing oxidative phosphorylation. This biosensor represents a unique tool to investigate carbon metabolism and bioenergetics in various cell types.

PMID:
26253029
DOI:
10.1016/j.molcel.2015.06.035
[Indexed for MEDLINE]
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