title: Translocase of outer mitochondrial membrane 70 expression is induced by hepatitis C virus and is related to the apoptotic response.
abstract: 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.
authors.affiliation: Faculty of Life Sciences, Department of Experimental Phylaxiology, Kumamoto University, Kumamoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takano
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kasama
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.forename: Chieko
authors.initials: C
authors.lastname: Kai
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsukiyama-Kohara
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000473:pathology / Q000821:virology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D033681:Mitochondrial Membrane Transport Proteins / Q000096:biosynthesis*; D051336:Mitochondrial Membranes / Q000201:enzymology*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C402118:TOMM70 protein, human