title: Hepatitis B virus X protein colocalizes to mitochondria with a human voltage-dependent anion channel, HVDAC3, and alters its transmembrane potential.
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.
authors.affiliation: Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Rahmani
authors.forename: K W
authors.initials: KW
authors.lastname: Huh
authors.forename: R
authors.initials: R
authors.lastname: Lasher
authors.forename: A
authors.initials: A
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D019556:COS Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism / Q000821:virology*; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D050994:Voltage-Dependent Anion Channels
chemical_list: D007473:Ion Channels; D018272:Porins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D050994:Voltage-Dependent Anion Channels; C057628:hepatitis B virus X protein