Peroxisomes are signaling platforms for antiviral innate immunity.
Peroxisomes are signaling platforms for antiviral innate immunity.
复制标题
DOI：
10.1016/j.cell.2010.04.018
复制
发表时间：
2010-05-14
期刊：
影响因子：
64.5
通讯作者：
Kagan JC
中科院分区：
文献类型：
--
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
过氧化物酶体在调节哺乳动物细胞的各种代谢活动中起着重要作用。这些细胞器与线粒体协同作用，控制脂质和活性氧的代谢。然而，虽然线粒体已成为抗病毒信号转导的重要场所，但过氧化物酶体在免疫防御中的作用尚不清楚。在这里，我们报告说，RIG-I样受体（RLR）衔接蛋白MAVS位于过氧化物酶体和线粒体。我们发现，过氧化物酶体和线粒体MAVS的作用顺序，创造一个抗病毒的细胞状态。在病毒感染后，过氧化物酶体MAVS诱导防御因子的快速干扰素非依赖性表达，提供短期保护，而线粒体MAVS激活具有延迟动力学的干扰素依赖性信号传导途径，其放大并稳定抗病毒应答。干扰素调节因子IRF 1在调节来自过氧化物酶体的MAVS依赖性信号传导中起关键作用。这些结果表明过氧化物酶体是抗病毒信号转导的重要位点。
Peroxisomes have long been established to play a central role in regulating various metabolic activities in mammalian cells. These organelles act in concert with mitochondria to control the metabolism of lipids and reactive oxygen species. However, while mitochondria have emerged as an important site of antiviral signal transduction, a role for peroxisomes in immune defense is unknown. Here, we report that the RIG-I-like receptor (RLR) adaptor protein MAVS is located on peroxisomes and mitochondria. We find that peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. The interferon regulatory factor IRF1 plays a crucial role in regulating MAVS-dependent signaling from peroxisomes. These results establish that peroxisomes are an important site of antiviral signal transduction.
登录
查看更多内容
DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
DOI：
10.1073/pnas.96.5.2116
发表时间：
1999-03-02
影响因子：
11.1
作者：
Matsuzono, Y;Kinoshita, N;Fujiki, Y
通讯作者：
Fujiki, Y
影响因子：
4.4
作者：
Balachandran, Siddharth;Venkataraman, Thiagarajan;Barber, Glen N.
通讯作者：
Barber, Glen N.
影响因子：
6.7
作者：
Cureton DK;Massol RH;Saffarian S;Kirchhausen TL;Whelan SP
通讯作者：
Whelan SP
影响因子：
30.5
作者：
通讯作者：
--