Hepatitis B Virus X Protein Colocalizes to Mitochondria with a Human Voltage-Dependent Anion Channel, HVDAC3, and Alters Its Transmembrane Potential
- 15 March 2000
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 74 (6), 2840-2846
- https://doi.org/10.1128/jvi.74.6.2840-2846.2000
Abstract
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.Keywords
This publication has 35 references indexed in Scilit:
- Bax and Adenine Nucleotide Translocator Cooperate in the Mitochondrial Control of ApoptosisScience, 1998
- Mitochondria and ApoptosisScience, 1998
- Analysis of mitochondrial morphology and function with novel fixable fluorescent stains.Journal of Histochemistry & Cytochemistry, 1996
- ATP Flux Is Controlled by a Voltage-gated Channel from the Mitochondrial Outer MembraneJournal of Biological Chemistry, 1996
- Induction of cell cycle progression by hepatitis B virus HBx gene expression in quiescent mouse fibroblasts.JCI Insight, 1994
- Human Genes Encoding the Voltage-Dependent Anion Channel (VDAC) of the Outer Mitochondrial Membrane: Mapping and Identification of Two New IsoformsGenomics, 1994
- Alterations in mitochondrial function and morphology in chronic liver disease: Pathogenesis and potential for therapeutic interventionPharmacology & Therapeutics, 1993
- Regulation of mitochondrial respiration by controlling the permeability of the outer membrane through the mitochondrial channel, VDACBiochimica et Biophysica Acta (BBA) - Bioenergetics, 1992
- Mouse Monoclonal Antibody Directed against Hepatitis B Virus X Protein Synthesized in Escherichia coli: Detection of Reactive Antigen in Liver Cell Carcinoma and Chronic HepatitisOncology, 1990
- HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS: A Prospective Study of 22 707 Men in TaiwanThe Lancet, 1981