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 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.
Lee
Young Ik
YI
Liver Cell Signal Transduction Laboratory, Laboratory, Bioscience Research Division, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, 305-600, Korea.
Hwang
Jung Me
JM
Im
Jee Hye
JH
Lee
Yoon Ik
YI
Kim
Nam Soon
NS
Kim
Dae Gon
DG
Yu
Dae Yeul
DY
Moon
Hyung Bae
HB
Park
Sook Kyung
SK
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004579:Electron Transport; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology*; D008113:Liver Neoplasms / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D016366:Open Reading Frames; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins; D051028:bcl-2-Associated X Protein
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D051028:bcl-2-Associated X Protein; C057628:hepatitis B virus X protein; D010100:Oxygen