title: HCV infection induces mitochondrial bioenergetic unbalance: causes and effects.
abstract: Cells infected by the hepatitis C virus (HCV) are characterized by endoplasmic reticulum stress, deregulation of the calcium homeostasis and unbalance of the oxido-reduction state. In this context, mitochondrial dysfunction proved to be involved and is thought to contribute to the outcome of the HCV-related disease. Here, we propose a temporal sequence of events in the HCV-infected cell whereby the primary alteration consists of a release of Ca(2+) from the endoplasmic reticulum, followed by uptake into mitochondria. This causes successive mitochondrial alterations comprising generation of reactive oxygen and nitrogen species and impairment of the oxidative phosphorylation. A progressive adaptive response results in an enhancement of the glycolytic metabolism sustained by up-regulation of the hypoxia inducible factor. Pathogenetic implications of the model are discussed.
authors.affiliation: Department of Biomedical Sciences, University of Foggia, 71100 Foggia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Piccoli
authors.forename: G
authors.initials: G
authors.lastname: Quarato
authors.forename: M
authors.initials: M
authors.lastname: Ripoli
authors.forename: A
authors.initials: A
authors.lastname: D'Aprile
authors.forename: R
authors.initials: R
authors.lastname: Scrima
authors.forename: O
authors.initials: O
authors.lastname: Cela
authors.forename: D
authors.initials: D
authors.lastname: Boffoli
authors.forename: D
authors.initials: D
authors.lastname: Moradpour
authors.forename: N
authors.initials: N
authors.lastname: Capitanio
mesh_terms: D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism; D016174:Hepacivirus / Q000378:metabolism; D006526:Hepatitis C / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009245:NADH Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation
chemical_list: D009245:NADH Dehydrogenase; D002118:Calcium