title: Mitochondrial dysfunction in hepatitis C.
abstract: Chronic hepatitis C induces a state of hepatic oxidative stress that is more pronounced than that present in many other inflammatory liver diseases. This review summarizes recent information that the hepatitis C virus (HCV) core protein plays an important role in this phenomenon. Core protein localizes to mitochondria, particularly at the points of contact between mitochondrial outer membrane and endoplasmic reticulum. Its expression causes inhibition of electron transport at complex I, increased complex I reactive oxygen species (ROS) production, decreased mitochondrial glutathione, and increased mitochondrial permeability transition in response to exogenous oxidants and tumor necrosis factor-alpha. Possible mechanisms of the core protein effects include direct interaction with electron carriers and indirect effects mediated by changes in mitochondrial calcium. These results suggest that antioxidant approaches may prove beneficial for patients with chronic hepatitis C.
authors.affiliation: Department of Internal Medicine University of Texas Medical Branch, Galveston, TX 77555-0641, USA.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Korenaga
authors.forename: Michiari
authors.initials: M
authors.lastname: Okuda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Otani
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.forename: Steven A
authors.initials: SA
authors.lastname: Weinman
mesh_terms: D016174:Hepacivirus / Q000378:metabolism; D006526:Hepatitis C / Q000503:physiopathology*; D006519:Hepatitis, Alcoholic / Q000503:physiopathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014758:Viral Core Proteins / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus