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Requirement of voltage-dependent anion channel 2 for pro-apoptotic activity of Bax

Oncogene volume 28, pages 3563–3572 (2009)Cite this article

An Erratum to this article was published on 13 May 2010

Abstract

Mitochondrial membrane permeabilization is central to apoptotic signaling and is directly regulated by the Bcl-2 family of proteins, consisting of anti-apoptotic members and pro-apoptotic members, although the precise mechanisms involved remain elusive. When cells are deficient in both pro-apoptotic multidomain members of this family (Bax and Bak), mitochondrial membrane permeabilization does not occur in response to various apoptotic stimuli. We have previously reported that the voltage-dependent anion channel (VDAC or porin) plays a role in apoptotic mitochondrial membrane permeabilization by interacting with Bcl-2 family members. Here, we have provided additional evidence that VDAC2 is required for pro-apoptotic activity of Bax in the absence of Bak. In the absence of Bak, VDAC2-deficient cells showed strong resistance to various apoptotic stimuli, whereas re-introduction of the Vdac2 gene restored their apoptotic response. Consistently, silencing of VDAC2 in Bak-deficient cells, but not Bax-deficient cells, also conferred resistance to various apoptotic stimuli. In the absence of VDAC2 and Bak, the activation of Bax (assessed by mitochondrial membrane integration, conformational changes and oligomerization) was markedly impaired. Taken together, these findings indicate that VDAC2 is required for pro-apoptotic activity of Bax in the absence of Bak.

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Acknowledgements

We are grateful to Dr Kitamura for providing of Plat-E cells. This study was supported in part by SORST of the Japan Science and Technology Corporation (JST), a grant for Creative Scientific Research from Japan Society for the Promotion of Science, a grant for the 21st Century COE Program from the Ministry of Education, Science, Sports and Culture, and a grant for Comprehensive Research on Aging and Health from the Ministry of Health, Labor and Welfare, Japan.

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Authors and Affiliations

  1. Department of Medical Genetics, Osaka University Medical School, Suita, Osaka, Japan,

    H Yamagata, S Shimizu, Y Nishida & Y Tsujimoto

  2. Department of Neuropsychiatry, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan,

    H Yamagata & Y Watanabe

  3. Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    S Shimizu & Y Nishida

  4. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    W J Craigen

  5. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    W J Craigen

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  1. H Yamagata
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  4. Y Watanabe
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Correspondence to Y Tsujimoto.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Yamagata, H., Shimizu, S., Nishida, Y. et al. Requirement of voltage-dependent anion channel 2 for pro-apoptotic activity of Bax. Oncogene 28, 3563–3572 (2009). https://doi.org/10.1038/onc.2009.213

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