Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential
Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential
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DOI：
10.1099/vir.0.057059-0
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发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Tikoo, Suresh K.
中科院分区：
文献类型：
--
作者：
Anand, Sanjeev K.;Gaba, Amit;Tikoo, Suresh K.
病毒通过将病毒蛋白质转运到线粒体来调节线粒体的功能。牛腺病毒（BAdV）-3感染/转染的细胞的线粒体组分的亚细胞分级分离和对蛋白酶K/Triton X-100处理的敏感性表明核心蛋白pVII定位于线粒体并且包含功能性线粒体定位信号。此外，BAdV-3 pVII的线粒体定位似乎有助于线粒体Ca 2+的保留，诱导ATP水平的显著增加并维持转染细胞中的线粒体膜电位（MMP）。相反，BAdV-3 pVII的线粒体定位对转染细胞中细胞质Ca 2+和活性氧产生的水平没有显著影响。与这些结果一致，在用星形孢菌素处理的转染细胞中表达pVII显著降低了半胱天冬酶-3的活化。我们的结果表明，BAdV-3 pVII定位于线粒体，并通过抑制MMP的损失和增加线粒体Ca 2+和ATP的产生来干扰凋亡。
Viruses modulate the functions of mitochondria by translocating viral proteins to the mitochondria. Subcellular fractionation and sensitivity to proteinase K/Triton X-100 treatment of mitochondria] fractions of bovine adenovirus (BAdV)-3-infected/transfected cells suggested that core protein pVII localizes to the mitochondria and contains a functional mitochondrial localization signal. Moreover, mitochondria] localization of BAdV-3 pVII appears to help in the retention of mitochondrial Ca2+, inducing a significant increase in the levels of ATP and maintaining the mitochondrial membrane potential (MMP) in transfected cells. In contrast, mitochondrial localization of BAdV-3 pVII has no significant effect on the levels of cytoplasmic Ca2+ and reactive oxygen species production in the transfected cells. Consistent with these results, expression of pVII in transfected cells treated with staurosporine decreased significantly the activation of caspase-3. Our results suggested that BAdV-3 pVII localizes to mitochondria, and interferes with apoptosis by inhibiting loss of the MMP and by increasing mitochondria] Ca2+ and ATP production.