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

Author

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  • 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
    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 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
    Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 149-153, 08036 Barcelona, Spain)

  • Tomer Shlomi

    (Technion, Israel Institute of Technology, Haifa 32000, Israel
    Lewis-Sigler Institute for Integrative Genomics, Princeton University)

  • 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)

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.

Suggested Citation

  • 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 Gottli, 2013. "A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence," Nature, Nature, vol. 498(7452), pages 109-112, June.
    • Handle: RePEc:nat:nature:v:498:y:2013:i:7452:d:10.1038_nature12154
    DOI: 10.1038/nature12154
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    Cited by:

    1. Martina Troiani & Manuel Colucci & Mariantonietta D’Ambrosio & Ilaria Guccini & Emiliano Pasquini & Angelica Varesi & Aurora Valdata & Simone Mosole & Ajinkya Revandkar & Giuseppe Attanasio & Andrea R, 2022. "Single-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Peng Liao & Long Chen & Hao Zhou & Jiong Mei & Ziming Chen & Bingqi Wang & Jerry Q. Feng & Guangyi Li & Sihan Tong & Jian Zhou & Siyuan Zhu & Yu Qian & Yao Zong & Weiguo Zou & Hao Li & Wenkan Zhang & , 2024. "Osteocyte mitochondria regulate angiogenesis of transcortical vessels," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Yinsheng Wu & Lixu Tang & Han Huang & Qi Yu & Bicheng Hu & Gang Wang & Feng Ge & Tailang Yin & Shanshan Li & Xilan Yu, 2023. "Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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