Proteomics Analysis of Mitochondrial Proteins Reveals Overexpression of a Mitochondrial Protein Chaperon, Prohibitin, in Cells Expressing Hepatitis C Virus Core Protein
Proteomics Analysis of Mitochondrial Proteins Reveals Overexpression of a Mitochondrial Protein Chaperon, Prohibitin, in Cells Expressing Hepatitis C Virus Core Protein
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DOI：
10.1002/hep.22998
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发表时间：
2009-08-01
期刊：
影响因子：
13.5
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
--
作者：
Tsutsumi, Takeya;Matsuda, Mami;Koike, Kazuhiko
丙型肝炎病毒核心蛋白参与了病毒的氧化应激诱导和脂质代谢紊乱等致病过程，主要定位于细胞质和内质网中，与脂滴和线粒体有关。为了阐明核心蛋白对线粒体的影响，我们用双向凝胶电泳法分析了线粒体蛋白在表达核心蛋白的细胞中的表达模式。用质谱仪鉴定了几种与线粒体呼吸链或蛋白伴侣相关的蛋白质。在已鉴定的差异表达的蛋白质中，线粒体蛋白伴侣Prohibitin不仅在核心表达细胞中上调，而且在核心基因转基因小鼠的全基因组复制子细胞和肝脏中也上调。通过与核心蛋白的相互作用，提高了禁忌素的稳定性。进一步的分析表明，禁止素与线粒体之间存在相互作用。DNA编码的细胞色素c氧化酶(COX)亚基受到核心蛋白的干扰，导致COX活性显著降低。结论：丙型肝炎病毒核心蛋白影响线粒体蛋白亚群的稳态水平，包括禁止蛋白，这可能导致线粒体呼吸链功能受损，导致氧化应激过度产生。(《肝病》2009；50：378-386。)
The hepatitis C virus (HC`V) core protein is involved in viral pathogenesis such as oxidative stress induction and lipid metabolism disturbance, and is primarily located in the cytoplasm and endoplasmic reticulum in association with lipid droplets as well as in the mitochondria. To clarify the impact of the core protein on mitochondria, we analyzed the expression pattern of mitochondrial proteins in core protein-expressing cells by two-dimensional polyacrylamide gel electrophoresis. Several proteins related to the mitochondrial respiratory chain or protein chaperons were identified by mass spectrometry. Among the identified proteins with consistently different expressions, prohibitin, a mitochondrial protein chaperon, was up-regulated not only in core-expressing cells but also in full-genomic replicon cells and livers of core-gene transgenic mice. The stability of prohibitin was increased through interaction with the core protein. Further analysis demonstrated that interaction of prohibitin with mitochondrial. DNA-encoded subunits of cytochrome c oxidase (COX) was disturbed by the core protein, resulting in a significant decrease in COX activity. Conclusion: The HCV core protein affects the steady-state levels of a subset of mitochondrial proteins including prohibitin, which may lead to an impaired function of the mitochondrial respiratory chain with the overproduction of oxidative stress. (HEPATOLOGY 2009;50:378-386.)