Emr1 调节内质网-线粒体遭遇结构复合物焦点的数量。
Emr1 regulates the number of foci of the endoplasmic reticulum-mitochondria encounter structure complex.
机构信息
Ministry of Education Key Laboratory for Membrane-less Organelles & Cellular Dynamics, CAS Center for Excellence in Molecular Cell Sciences, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230027, Hefei, People's Republic of China.
出版信息
Nat Commun. 2021 Jan 22;12(1):521. doi: 10.1038/s41467-020-20866-x.
The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex creates contact sites between the endoplasmic reticulum and mitochondria, playing crucial roles in interorganelle communication, mitochondrial fission, mtDNA inheritance, lipid transfer, and autophagy. The mechanism regulating the number of ERMES foci within the cell remains unclear. Here, we demonstrate that the mitochondrial membrane protein Emr1 contributes to regulating the number of ERMES foci. We show that the absence of Emr1 significantly decreases the number of ERMES foci. Moreover, we find that Emr1 interacts with the ERMES core component Mdm12 and colocalizes with Mdm12 on mitochondria. Similar to ERMES mutant cells, cells lacking Emr1 display defective mitochondrial morphology and impaired mitochondrial segregation, which can be rescued by an artificial tether capable of linking the endoplasmic reticulum and mitochondria. We further demonstrate that the cytoplasmic region of Emr1 is required for regulating the number of ERMES foci. This work thus reveals a crucial regulatory protein necessary for ERMES functions and provides mechanistic insights into understanding the dynamic regulation of endoplasmic reticulum-mitochondria communication.
内质网-线粒体接触结构(ERMES)复合物在细胞器间通讯、线粒体裂变、mtDNA 遗传、脂质转移和自噬中创建内质网和线粒体之间的接触位点,发挥着关键作用。调节细胞内 ERMES 焦点数量的机制尚不清楚。在这里,我们证明了线粒体膜蛋白 Emr1 有助于调节 ERMES 焦点的数量。我们发现 Emr1 的缺失显著减少了 ERMES 焦点的数量。此外,我们发现 Emr1 与 ERMES 核心成分 Mdm12 相互作用,并与 Mdm12 在线粒体上共定位。类似于 ERMES 突变细胞,缺乏 Emr1 的细胞显示出线粒体形态缺陷和线粒体分离受损,这可以通过能够连接内质网和线粒体的人工系绳来挽救。我们进一步证明,Emr1 的细胞质区域对于调节 ERMES 焦点的数量是必需的。这项工作因此揭示了 ERMES 功能所必需的关键调节蛋白,并为理解内质网-线粒体通讯的动态调节提供了机制上的见解。