Translocase of Outer Mitochondrial Membrane 70 Expression Is Induced by Hepatitis C Virus and Is Related to the Apoptotic Response

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-alpha)-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. (C) 2011 Wiley-Liss, Inc.