Dengue virus induces mitochondrial elongation through impairment of Drp1-triggered mitochondrial fission.
Dengue virus induces mitochondrial elongation through impairment of Drp1-triggered mitochondrial fission.
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DOI：
10.1016/j.virol.2016.10.022
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发表时间：
2017-01
期刊：
影响因子：
3.7
通讯作者：
Medin, Carey L.
中科院分区：
文献类型：
--
作者：
Barbier, Vincent;Lang, Diane;Valois, Sierra;Rothman, Alan L.;Medin, Carey L.
线粒体是高度动态的细胞器，其经历连续的分裂和融合循环以维持基本的细胞功能。这两个过程之间的不平衡可能导致许多病理生理结果。登革病毒（DENV）与细胞器（包括线粒体）相互作用以在细胞中成功复制。这项研究使用活细胞成像，发现DENV感染期间线粒体长度和呼吸增加。在DENV感染期间，线粒体上的线粒体分裂蛋白，动力蛋白相关蛋白1（Drp1）的水平降低，并且Drp1在丝氨酸616上磷酸化，这对于线粒体分裂是重要的。病毒蛋白NS4b和NS3也与线粒体的亚细胞组分相关。通过线粒体解偶联或过表达Drp1野生型和具有磷酸化突变（S616D）的Drp1诱导分裂显著降低病毒复制。这些结果表明，DENV感染通过抑制Drp1触发的线粒体分裂而导致线粒体动力学失衡，这促进了病毒复制。
Mitochondria are highly dynamic organelles that undergo continuous cycles of fission and fusion to maintain essential cellular functions. An imbalance between these two processes can result in many pathophysiological outcomes. Dengue virus (DENV) interacts with cellular organelles, including mitochondria, to successfully replicate in cells. This study used live-cell imaging and found an increase in mitochondrial length and respiration during DENV infection. The level of mitochondrial fission protein, Dynamin-related protein 1 (Drp1), was decreased on mitochondria during DENV infection, as well as Drp1 phosphorylated on serine 616, which is important for mitochondrial fission. Viral proteins NS4b and NS3 were also associated with subcellular fractions of mitochondria. Induction of fission through uncoupling of mitochondria or overexpression of Drp1 wild-type and Drp1 with a phosphomimetic mutation (S616D) significantly reduced viral replication. These results demonstrate that DENV infection causes an imbalance in mitochondrial dynamics by inhibiting Drp1-triggered mitochondrial fission, which promotes viral replication.
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影响因子：
3.5
作者：
Chen H;Chan DC
通讯作者：
Chan DC
影响因子：
7.8
作者：
Detmer, Scott A;Chan, David C
通讯作者：
Chan, David C
影响因子：
3.3
作者：
Couvelard, A;Marianneau, P;Deubel, V
通讯作者：
Deubel, V
DOI：
10.1073/pnas.0703348104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Emara, Mohamed M.;Brinton, Margo A.
通讯作者：
Brinton, Margo A.
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC