An N-terminal addressing sequence targets NLRX1 to the mitochondrial matrix
An N-terminal addressing sequence targets NLRX1 to the mitochondrial matrix
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DOI：
10.1242/jcs.051193
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Girardin, Stephen E.
中科院分区：
文献类型：
--
作者：
Arnoult, Damien;Soares, Fraser;Girardin, Stephen E.
NLRX 1是Nod样受体（NLR）家族中唯一靶向线粒体的成员，其过表达诱导活性氧（ROS）的产生，从而影响NF κ B和JNK依赖性信号级联。此外，NLRX 1已被证明与MAVS（也称为IPS-1，VISA和Cardif）在线粒体外膜相互作用，并调节抗病毒反应。在这里，我们报告说，NLRX 1有一个功能性的前导序列，并完全易位到线粒体基质通过一种机制，需要线粒体内膜电位，Δ Psim。重要的是，我们未能在线粒体外膜检测到NLRX 1。我们还表明，NLRX 1的前导序列被删除，这产生了一个成熟的蛋白质缺乏前39个氨基酸，通过成熟过程，这是常见的尿道基质蛋白。最后，我们确定了UQCRC 2，呼吸链复合物III的一种基质蛋白，作为NLRX 1相互作用分子，从而为NLRX 1在ROS生成中的作用提供了分子基础。这些结果提供了属于NLR家族的蛋白质的第一个鉴定，该蛋白质靶向线粒体基质。
NLRX1 is the only member of the Nod-like receptor (NLR) family that is targeted to the mitochondria, and its overexpression induces the generation of reactive oxygen species (ROS), thus impacting on NF kappa B- and JNK-dependent signaling cascades. In addition, NLRX1 has been shown to interact with MAVS (also known as IPS-1, VISA and Cardif) at the mitochondrial outer membrane and to modulate antiviral responses. Here we report that NLRX1 has a functional leader sequence and fully translocates to the mitochondrial matrix via a mechanism requiring the mitochondrial inner-membrane potential,Delta Psi m. Importantly, we failed to detect NLRX1 at the mitochondrial outer membrane. We also show that the leader sequence of NLRX1 is removed, which generates a mature protein lacking the first 39 amino acids through a maturation process that is common for mitochondrial-matrix proteins. Finally, we identified UQCRC2, a matrix-facing protein of the respiratory chain complex III, as an NLRX1-interacting molecule, thus providing a molecular basis for the role of NLRX1 in ROS generation. These results provide the first identification of a protein belonging to the NLR family that is targeted to the mitochondrial matrix.