Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity.
FASEB J
; 21(10): 2474-85, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17392480
ABSTRACT
Many viruses have evolved mechanisms to alter mitochondrial function. The hepatitis C virus (HCV) produces a viral core protein that targets to mitochondria and increases Ca2+-dependent ROS production. The aim of this study was to determine whether core's effects are mediated by changes in mitochondrial Ca2+ uptake. Core expression caused enhanced mitochondrial Ca2+ uptake in response to ER Ca2+ release induced by thapsigargin or ATP. It also increased mitochondrial superoxide production and mitochondrial permeability transition (MPT). Incubating mouse liver mitochondria with an HCV core (100 ng/mg) in vitro increased Ca2+ entry rate by approximately 2-fold. Entry was entirely inhibited by the mitochondrial Ca2+ uniporter inhibitor, Ru-360, but not influenced by an Na+/Ca2+ exchanger inhibitor or ROS scavengers. These results indicate that core directly increases mitochondrial Ca2+ uptake via a primary effect on the uniporter. This enhanced the ability of mitochondria to sequester Ca2+ in response to ER Ca2+ release, and increased mitochondrial ROS production and MPT. Thus, the mitochondrial Ca2+ uniporter is a newly identified target for viral modification of cell function.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mitocôndrias Hepáticas
/
Proteínas do Core Viral
/
Cálcio
/
Espécies Reativas de Oxigênio
/
Antiporters
/
Antígenos da Hepatite C
/
Proteínas de Transporte de Cátions
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos