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Translocase of outer mitochondrial membrane 70 expression is induced by hepatitis C virus and is related to the apoptotic response
Author(s) -
Takano Takashi,
Kohara Michinori,
Kasama Yuri,
Nishimura Tomohiro,
Saito Makoto,
Kai Chieko,
TsukiyamaKohara Kyoko
Publication year - 2011
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.22046
Subject(s) - ns3 , apoptosis , biology , gene silencing , microbiology and biotechnology , mitochondrion , cytochrome c , bacterial outer membrane , chemistry , virology , hepatitis c virus , biochemistry , virus , gene , escherichia coli
The localization of hepatitis C virus (HCV) proteins in cells leads to several problems. The translocase of outer mitochondrial membrane 70 (TOM70) is a mitochondrial import receptor. In this study, TOM70 expression was induced by HCV infection. TOM70 overexpression induced resistance to tumor necrosis factor‐alpha (TNF‐α)‐mediated apoptosis but not to Fas‐induced apoptosis in HepG2 cells. TOM70 was found to be induced by the HCV non‐structural protein (NS)3/4A protein, and silencing of TOM70 decreased the levels of the NS3 and Mcl‐1 proteins. These results indicate that TOM70 can directly interact with the NS3 protein. In hepatoma cells, silencing of TOM70 induced apoptosis and increased caspase‐3/7 activity but did not modify caspase‐8 and caspase‐9 activity. TOM70 silencing‐induced apoptosis was impaired in HCV NS3/4A protein‐expressing cells. Thus, this study revealed a novel finding, that is, TOM70 is linked with the NS3 protein and the apoptotic response. J. Med. Virol. 83:801–809, 2011. © 2011 Wiley‐Liss, Inc.