期刊
MOLECULAR CELL
卷 59, 期 3, 页码 491-501出版社
CELL PRESS
DOI: 10.1016/j.molcel.2015.06.035
关键词
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资金
- Marie Curie Intra European Fellowship
- Institut National de la Sante et de la Recherche Medicale
- Ligue Nationale Contre le Cancer
- Ligue Nationale Contre le Cancer (Equipe labellisee LNCC)
- Swiss National Science Foundation [31993A-141068/1]
- Sinergia [CRSII3_147637]
- IGE3
- State of Geneva
- Ligue Genevoise Contre le Cancer
- Swiss National Science Foundation (SNF) [CRSII3_147637] Funding Source: Swiss National Science Foundation (SNF)
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.
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