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Bmi1 regulates mitochondrial function and the DNA damage response pathway

Author

Listed:
  • Jie Liu

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Liu Cao

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Jichun Chen

    (Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Shiwei Song

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • In Hye Lee

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Celia Quijano

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Hongjun Liu

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Keyvan Keyvanfar

    (Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Haoqian Chen

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Long-Yue Cao

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Bong-Hyun Ahn

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Neil G. Kumar

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,
    Howard Hughes Medical Institute, NIH Research Scholar Program,)

  • Ilsa I. Rovira

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

  • Xiao-Ling Xu

    (Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Maarten van Lohuizen

    (Netherlands Cancer Institute and Centre for Biomedical Genetics)

  • Noboru Motoyama

    (National Institute for Longevity Sciences National Center for Geriatrics and Gerontology 36-3, Gengo, Morioka, Obu, Aichi 474-8522, Japan)

  • Chu-Xia Deng

    (Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Toren Finkel

    (Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health,)

Abstract

Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities including a severe defect in stem cell self-renewal, alterations in thymocyte maturation and a shortened lifespan. Previous work has implicated de-repression of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of the Bmi1-/- phenotype. Here we demonstrate that cells derived from Bmi1-/- mice also have impaired mitochondrial function, a marked increase in the intracellular levels of reactive oxygen species and subsequent engagement of the DNA damage response pathway. Furthermore, many of the deficiencies normally observed in Bmi1-/- mice improve after either pharmacological treatment with the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that Bmi1 has an unexpected role in maintaining mitochondrial function and redox homeostasis and indicate that the Polycomb family of proteins can coordinately regulate cellular metabolism with stem and progenitor cell function.

Suggested Citation

  • Jie Liu & Liu Cao & Jichun Chen & Shiwei Song & In Hye Lee & Celia Quijano & Hongjun Liu & Keyvan Keyvanfar & Haoqian Chen & Long-Yue Cao & Bong-Hyun Ahn & Neil G. Kumar & Ilsa I. Rovira & Xiao-Ling X, 2009. "Bmi1 regulates mitochondrial function and the DNA damage response pathway," Nature, Nature, vol. 459(7245), pages 387-392, May.
    • Handle: RePEc:nat:nature:v:459:y:2009:i:7245:d:10.1038_nature08040
    DOI: 10.1038/nature08040
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