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Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death

Oncogene volume 18, pages 6965–6973 (1999)Cite this article

Abstract

Hepatitis B virus (HBV) X protein activates many viral and cellular genes in trans and functional disruption of the p53 tumor suppressor gene product occurs when X protein is transiently expressed in the cytoplasm of cultured cells. We have carried out investigations to determine the exact location of X protein in X gene transfected cells by using a fluorescent staining technique as well as by biochemical analyses. Aggregation of mitochondrial structures became evident at the periphery of nucleus in the cytoplasm of X transfected cells. X protein was found associated with the aggregated mitochondrial structures. Furthermore, transiently expressed p53 protein co-localized with X protein in X transfected cells. However, the appearance of aggregated mitochondrial structures at the nuclear periphery was independent of the presence of p53 protein in X transfected cells. X protein expression also caused an appearance of TUNEL positive nucleus, cytochrome c release from mitochondrial, the decrease of mitochondrial membrane potential and the membrane blebbing of X transfected cells, which are characteristic of cell death. Our data suggest that X protein causes an abnormal aggregation of mitochondrial structures in the cell, which may be eventually connected with cell death.

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Acknowledgements

We thank VP Iyemere for reading the manuscript and M Kobayashi for preparing the manuscript. This work was supported partly by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture and a Grant-in-Aid from the Ministry of Health and Welfare, Japan to K Koike. The work was also supported partly by a grant from Mitsui Life Social Welfare Foundation, Tokyo, Japan to K Koike.

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  1. Shinako Takada

    Present address: Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, University of California, Berkeley, California, CA 94720, USA

  2. Shinako Takada: S Takada and Y Shirakata contributed equally to this work

Authors and Affiliations

  1. Department of Gene Research, The Cancer Institute, (JFCR), Kami-Ikebukuro, Toshima-ku, Tokyo, 170-8455, Japan

    Shinako Takada, Yumiko Shirakata, Noriko Kaneniwa & Katsuro Koike

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  1. Shinako Takada
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Takada, S., Shirakata, Y., Kaneniwa, N. et al. Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death. Oncogene 18, 6965–6973 (1999). https://doi.org/10.1038/sj.onc.1203188

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