Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity

Yanchun Li, Darren F. Boehning, Ting Qian, Vsevolod Popov, Steven A. Weinman

Research output: Contribution to journalArticle

113 Citations (Scopus)

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 Ca 2+ entry rate by ∼ 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.

Original languageEnglish (US)
Pages (from-to)2474-2485
Number of pages12
JournalFASEB Journal
Volume21
Issue number10
DOIs
StatePublished - Aug 2007

Fingerprint

Mitochondria
Hepatitis C virus
Viruses
Hepacivirus
Permeability
Viral Core Proteins
calcium
Thapsigargin
Liver Mitochondrion
Superoxides
proteins
Adenosine Triphosphate
Liver
mitochondria
uptake mechanisms
permeability
Hepatitis C virus nucleocapsid protein
superoxide anion
In Vitro Techniques
Ru 360

Keywords

  • Ca
  • HCV core
  • MAVS
  • Mitochondria cytosolic

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity. / Li, Yanchun; Boehning, Darren F.; Qian, Ting; Popov, Vsevolod; Weinman, Steven A.

In: FASEB Journal, Vol. 21, No. 10, 08.2007, p. 2474-2485.

Research output: Contribution to journalArticle

Li, Yanchun ; Boehning, Darren F. ; Qian, Ting ; Popov, Vsevolod ; Weinman, Steven A. / Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity. In: FASEB Journal. 2007 ; Vol. 21, No. 10. pp. 2474-2485.
@article{623bd5f7c1d64bd9a1bf0cd2962bdaff,
title = "Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity",
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 Ca 2+ entry rate by ∼ 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.",
keywords = "Ca, HCV core, MAVS, Mitochondria cytosolic",
author = "Yanchun Li and Boehning, {Darren F.} and Ting Qian and Vsevolod Popov and Weinman, {Steven A.}",
year = "2007",
month = "8",
doi = "10.1096/fj.06-7345com",
language = "English (US)",
volume = "21",
pages = "2474--2485",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "10",

}

TY - JOUR

T1 - Hepatitis C virus core protein increases mitochondrial ROS production by stimulation of Ca2+ uniporter activity

AU - Li, Yanchun

AU - Boehning, Darren F.

AU - Qian, Ting

AU - Popov, Vsevolod

AU - Weinman, Steven A.

PY - 2007/8

Y1 - 2007/8

N2 - 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 Ca 2+ entry rate by ∼ 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.

AB - 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 Ca 2+ entry rate by ∼ 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.

KW - Ca

KW - HCV core

KW - MAVS

KW - Mitochondria cytosolic

UR - http://www.scopus.com/inward/record.url?scp=34547739644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547739644&partnerID=8YFLogxK

U2 - 10.1096/fj.06-7345com

DO - 10.1096/fj.06-7345com

M3 - Article

VL - 21

SP - 2474

EP - 2485

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 10

ER -