Proteomics analysis of mitochondrial proteins reveals overexpression of a mitochondrial protein chaperon, prohibitin, in cells expressing hepatitis C virus core protein
- 9 July 2009
- journal article
- viral hepatitis
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 50 (2), 378-386
- https://doi.org/10.1002/hep.22998
Abstract
The hepatitis C virus (HCV) core protein is involved in viral pathogenesis such as oxidative stress induction and lipid metabolism disturbance, and is primarily located in the cytoplasm and endoplasmic reticulum in association with lipid droplets as well as in the mitochondria. To clarify the impact of the core protein on mitochondria, we analyzed the expression pattern of mitochondrial proteins in core protein-expressing cells by two-dimensional polyacrylamide gel electrophoresis. Several proteins related to the mitochondrial respiratory chain or protein chaperons were identified by mass spectrometry. Among the identified proteins with consistently different expressions, prohibitin, a mitochondrial protein chaperon, was up-regulated not only in core-expressing cells but also in full-genomic replicon cells and livers of core-gene transgenic mice. The stability of prohibitin was increased through interaction with the core protein. Further analysis demonstrated that interaction of prohibitin with mitochondrial DNA-encoded subunits of cytochrome c oxidase (COX) was disturbed by the core protein, resulting in a significant decrease in COX activity. The HCV core protein affects the steady-state levels of a subset of mitochondrial proteins including prohibitin, which may lead to an impaired function of the mitochondrial respiratory chain with the overproduction of oxidative stress.Keywords
This publication has 36 references indexed in Scilit:
- Proteomic profiling of human liver biopsies: Hepatitis C virus-induced fibrosis and mitochondrial dysfunctionHepatology, 2007
- Hepatitis C Virus Triggers Mitochondrial Permeability Transition with Production of Reactive Oxygen Species, Leading to DNA Damage and STAT3 ActivationJournal of Virology, 2006
- Hepatitis C Virus Core Protein Inhibits Mitochondrial Electron Transport and Increases Reactive Oxygen Species (ROS) ProductionJournal of Biological Chemistry, 2005
- Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2Journal of General Virology, 2005
- Molecular Determinants for Subcellular Localization of Hepatitis C Virus Core ProteinJournal of Virology, 2005
- Targeting of Hepatitis C Virus Core Protein to Mitochondria through a Novel C-Terminal Localization MotifJournal of Virology, 2004
- Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core proteinGastroenterology, 2002
- Processing and Functions of Hepatitis C Virus ProteinsIntervirology, 1999
- The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic miceNature Medicine, 1998
- Hepatitis C virus core protein induces hepatic steatosis in transgenic mice.Journal of General Virology, 1997