2. Academic Validation
  3. The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase

The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase

  • Cell Metab. 2013 Jun 4;17(6):988-999. doi: 10.1016/j.cmet.2013.04.019.
Marco Sciacovelli 1,  Giulia Guzzo 1,  Virginia Morello 2,  Christian Frezza 3,  Liang Zheng 4,  Nazarena Nannini 5,  Fiorella Calabrese 5,  Gabriella Laudiero 6,  Franca Esposito 6,  Matteo Landriscina 7,  Paola Defilippi 2,  Paolo Bernardi 8,  Andrea Rasola 9
Affiliations

Affiliations

  • 1 CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy.
  • 2 Molecular Biotechnology Centre, Department of Genetics, Biology and Biochemistry, University of Torino, 10125 Torino, Italy.
  • 3 Cancer Research United Kingdom, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
  • 4 Cancer Research United Kingdom, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G61 1BD, UK.
  • 5 Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, 35121 Padova, Italy.
  • 6 Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, 80131 Napoli, Italy.
  • 7 Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
  • 8 CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy. Electronic address: [email protected].
  • 9 CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy. Electronic address: [email protected].
PMID: 23747254 DOI: 10.1016/j.cmet.2013.04.019
Abstract

We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target.

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