Targeting mitochondria in the infection strategy of the hepatitis C virus.
Hepatitis C virus (HCV) infection induces a state of oxidative stress more pronounced than that observed in many other inflammatory diseases. 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 ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen species and a progressive metabolic adaptive response. Evidence is provided for a positive feed-back mechanism between alterations of calcium and redox homeostasis. This likely involves deregulation of the mitochondrial permeability transition and induces progressive dysfunction of cellular bioenergetics. Pathogenetic implications of the model and new opportunities for therapeutic intervention are discussed. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.
Department of Biomedical Sciences, University of Foggia, Foggia, Italy.
Giovanni
G
Quarato
Rosella
R
Scrima
Francesca
F
Agriesti
Darius
D
Moradpour
Nazzareno
N
Capitanio
Claudia
C
Piccoli
D000818:Animals; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D014764:Viral Proteins / Q000235:genetics
D014764:Viral Proteins