Human Hepatitis B Virus-X Protein Alters Mitochondrial Function and Physiology in Human Liver Cells

The hepatitis B virus-X protein (HBx) regulates fundamental aspects of mitochondrial physiology. We show that HBx down-regulates mitochondrial enzymes involved in electron transport in oxidative phosphorylation (complexes I, III, IV, and V) and sensitizes the mitochondrial membrane potential in a he...

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Published inThe Journal of biological chemistry Vol. 279; no. 15; pp. 15460 - 15471
Main Authors Lee, Young Ik, Hwang, Jung Me, Im, Jee Hye, Lee, Yoon Ik, Kim, Nam Soon, Kim, Dae Gon, Yu, Dae Yeul, Moon, Hyung Bae, Park, Sook Kyung
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 09.04.2004
American Society for Biochemistry and Molecular Biology
Subjects
Animals
Apoptosis
bcl-2-Associated X Protein
Blotting, Northern
Blotting, Western
Carcinoma, Hepatocellular - metabolism
Cell Line, Tumor
Down-Regulation
Electron Transport
Flow Cytometry
Gene Expression Profiling
Hepatitis B virus
Hepatitis B virus - metabolism
Humans
In Situ Nick-End Labeling
Lipid Metabolism
Lipid Peroxidation
Liver - cytology
Liver Neoplasms - metabolism
Mice
Mice, Transgenic
Microscopy, Fluorescence
Mitochondria - metabolism
Mitochondria - physiology
Open Reading Frames
Oxygen - metabolism
Phosphorylation
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2
Reactive Oxygen Species
Signal Transduction
Trans-Activators - physiology
Viral Regulatory and Accessory Proteins
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Summary:The hepatitis B virus-X protein (HBx) regulates fundamental aspects of mitochondrial physiology. We show that HBx down-regulates mitochondrial enzymes involved in electron transport in oxidative phosphorylation (complexes I, III, IV, and V) and sensitizes the mitochondrial membrane potential in a hepatoma cell line. HBx also increases the level of mitochondrial reactive oxygen species and lipid peroxide production. HBx does not activate apoptotic signaling, although it sensitizes hepatoma cells to apoptotic signaling, which is dependent on reactive oxygen species. Increased intrahepatic lipid peroxidation in HBx transgenic mice demonstrated that oxidative injury occurs as a direct result of HBx expression. Therefore, we conclude that mitochondrial dysfunction is a crucial pathophysiological factor in HBx-expressing hepatoma cells and provides an experimental rationale in the investigation of mitochondrial function in rapidly renewed tissues, as in hepatocellular carcinomas.
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ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M309280200