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Journal of Virology, March 2000, p. 2840-2846, Vol. 74, No. 6
0022-538X/00/$04.00+0

Hepatitis B Virus X Protein Colocalizes to Mitochondria with a Human Voltage-Dependent Anion Channel, HVDAC3, and Alters Its Transmembrane Potential

Zohra Rahmani,1,dagger Kyung-Won Huh,1 Robert Lasher,2 and Aleem Siddiqui1,*

Department of Microbiology1 and Department of Cellular and Structural Biology,2 University of Colorado Health Sciences Center, Denver, Colorado 80262

Received 9 August 1999/Accepted 7 December 1999

Understanding the mechanism(s) of action of the hepatitis B virus (HBV)-encoded protein HBx is fundamental to elucidating the underlying mechanisms of chronic liver disease and hepatocellular carcinoma caused by HBV infection. In our continued attempts to identify cellular targets of HBx, we have previously reported the identification of a novel cellular protein with the aid of a yeast two-hybrid assay. This cellular gene was identified as a third member of the family of human genes that encode the voltage-dependent anion channel (HVDAC3). In the present study, physical interaction between HBx and HVDAC3 was established by standard in vitro and in vivo methods. Confocal laser microscopy of transfected cells with respective expression vectors colocalized HVDAC3 and HBx to mitochondria. This novel, heretofore unreported subcellular distribution of HBx in mitochondria implies a functional role of HBx in functions associated with mitochondria. Using a stable cationic fluorophore dye, CMXRos, we show that HBx expression in cultured human hepatoma cells leads to alteration of mitochondrial transmembrane potential. Such functional roles of HBx in affecting mitochondrial physiology have implications for HBV-induced liver injury and the development of hepatocellular carcinoma.

* Corresponding author. Mailing address: Department of Microbiology, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262. Phone: (303) 315-7016. Fax: (303) 315-8330. E-mail: Aleem.Siddiqui{at}UCHSC.edu.

dagger Present address: Hopital Necker-enfants Malades, Faculte de Medicine, CNRS URA 1335, 75730 Paris Cedex 15, France.

Journal of Virology, March 2000, p. 2840-2846, Vol. 74, No. 6
0022-538X/00/$04.00+0


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