Scientific article
Open access

Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis

Publication date2013

TRAP1 (TNF receptor-associated protein), a member of the HSP90 chaperone family, is found predominantly in mitochondria. TRAP1 is broadly considered to be an anticancer molecular target. However, current inhibitors cannot distinguish between HSP90 and TRAP1, making their utility as probes of TRAP1-specific function questionable. Some cancers express less TRAP1 than do their normal tissue counterparts, suggesting that TRAP1 function in mitochondria of normal and transformed cells is more complex than previously appreciated. We have used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1-deficiency promotes an increase in mitochondrial respiration and fatty acid oxidation, and in cellular accumulation of tricarboxylic acid cycle intermediates, ATP and reactive oxygen species. At the same time, glucose metabolism is suppressed. TRAP1-deficient cells also display strikingly enhanced invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes. Taken together with the observation that TRAP1 expression is inversely correlated with tumor grade in several cancers, these data suggest that, in some settings, this mitochondrial molecular chaperone may act as a tumor suppressor.

  • Animals
  • COS Cells
  • Cercopithecus aethiops
  • Glycolysis
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins/genetics/metabolism
  • Mice
  • Mice, Knockout
  • Mitochondria/metabolism
  • Mitochondrial Proteins/genetics/metabolism
  • Molecular Chaperones/genetics/metabolism
  • NIH 3T3 Cells
  • Neoplasm Invasiveness/genetics
  • Oxidative Phosphorylation
  • RNA Interference
  • Transfection
  • Src-Family Kinases/metabolism
Research group
Citation (ISO format)
YOSHIDA, Soichiro et al. Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis. In: Proceedings of the National Academy of Sciences of the United States of America, 2013, vol. 110, n° 17, p. E1604–1612. doi: 10.1073/pnas.1220659110
Main files (1)
Article (Published version)
ISSN of the journal0027-8424

Technical informations

Creation10/22/2013 6:21:00 PM
First validation10/22/2013 6:21:00 PM
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