Redox Nanodomains Are Induced by and Control Calcium Signaling at the ER-Mitochondrial Interface.
Redox Nanodomains Are Induced by and Control Calcium Signaling at the ER-Mitochondrial Interface.
复制标题
氧化还原纳米域受ER-线粒体界面的钙信号诱导和控制
DOI：
10.1016/j.molcel.2016.05.040
复制
发表时间：
2016-07-21
期刊：
影响因子：
16
通讯作者：
Hajnóczky G
中科院分区：
文献类型：
--
作者：
Booth DM;Enyedi B;Geiszt M;Várnai P;Hajnóczky G
er -线粒体界面是钙信号传导、细胞器动力学和脂质生物合成的中心。内质网和线粒体膜也承载活性氧（ROS）的来源和靶标，但它们的局部动力学和相关性仍然难以捉摸，因为在细胞器界面测量和扰动ROS已被证明是困难的。利用药物诱导的合成er -线粒体连接体，我们克服了这一问题，并证明er -线粒体界面拥有H2O2纳米结构域，H2O2由细胞质[Ca2+]峰值诱导，并对钙振荡施加正反馈。H2O2纳米结构域起源于线粒体嵴，在钙信号传播到线粒体时被压缩，可能是由于Ca2+诱导的K+和伴随的水流入基质。因此，er-线粒体H2O2纳米结构域代表了细胞器间通信的新组成部分，调节钙信号和线粒体活动。在Ca2+信号期间，升高的Ca2+微域在er -线粒体界面形成。在这里，Booth等人证明H2O2的纳米结构域也存在。这是由Ca2+诱导的线粒体嵴活性氧的动员产生的，其功能是使内质网Ca2+通道敏感。
The ER-mitochondrial interface is central to calcium signaling, organellar dynamics and lipid biosynthesis. The ER and mitochondrial membranes also host sources and targets of reactive oxygen species (ROS) but their local dynamics and relevance remained elusive since measurement and perturbation of ROS at the organellar interface has proven difficult. Employing drug-inducible synthetic ER-mitochondrial linkers, we overcame this problem and demonstrate that the ER-mitochondrial interface hosts a nanodomain of H2O2, which is induced by cytoplasmic [Ca2+] spikes and exert a positive feedback on calcium oscillations. H2O2 nanodomains originate from the mitochondrial cristae, which are compressed upon calcium signal propagation to the mitochondria, likely due to Ca2+-induced K+ and concomitant water influx to the matrix. Thus, ER-mitochondrial H2O2 nanodomains represent a novel component of inter-organelle communication, regulating calcium signaling and mitochondrial activities. During Ca2+ signals, elevated Ca2+ microdomains form at the ER-mitochondrial interface. Here, Booth et al. demonstrate that a nanodomain of H2O2 is also present. This is produced by Ca2+ induced mobilization of ROS from the mitochondrial cristae and functions to sensitize ER Ca2+ channels.