A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence

Joanna Kaplon, Liang Zheng, Katrin Meissl, Barbara Chaneton, Vitaly A. Selivanov, Gillian Mackay, Sjoerd H. van der Burg, Elizabeth M. E. Verdegaal, Marta Cascante, Tomer Shlomi, Eyal Gottlieb () and Daniel S. Peeper ()
Additional contact information
Joanna Kaplon: The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Liang Zheng: Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
Katrin Meissl: The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Barbara Chaneton: Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
Vitaly A. Selivanov: Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028 Barcelona, Spain
Gillian Mackay: Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
Sjoerd H. van der Burg: Experimental Cancer Immunology and Therapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Elizabeth M. E. Verdegaal: Experimental Cancer Immunology and Therapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Marta Cascante: Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028 Barcelona, Spain
Tomer Shlomi: Technion, Israel Institute of Technology, Haifa 32000, Israel
Eyal Gottlieb: Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
Daniel S. Peeper: The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

Nature, 2013, vol. 498, issue 7452, 109-112

Abstract: Pyruvate dehydrogenase (PDH) is identified as a crucial mediator of BRAFV600E-induced cellular senescence: PDH is activated by BRAF-mediated suppression of PDK1, enhancing oxidative glucose metabolism, and PDK1 depletion eradicates mutant BRAF melanomas, indicating that this relationship between cell senescence and metabolism might be exploited therapeutically.

Date: 2013
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DOI: 10.1038/nature12154

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