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Journal of Virology, March 2000, p. 2840-2846, Vol. 74, No. 6
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.
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

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