Bmi1 regulates mitochondrial function and the DNA damage response pathway

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 Xu, Maarten Van Lohuizen, Noboru Motoyama, Chu Xia Deng, Toren Finkel

Research output: Contribution to journalArticlepeer-review

400 Scopus citations


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.

Original languageEnglish
Pages (from-to)387-392
Number of pages6
Issue number7245
StatePublished - 21 May 2009

Bibliographical note

Funding Information:
Acknowledgements We are grateful to M. Clarke for providing the initial supply of Bmi12/2 mice, to J. Moss for the gift of anti-PARP antibodies and to M. Daniels and the NHLBI electron microscope core for their assistance. This work was supported by funding from the NIH intramural program and the Ellison Medical Foundation.


Dive into the research topics of 'Bmi1 regulates mitochondrial function and the DNA damage response pathway'. Together they form a unique fingerprint.

Cite this