Wu Wenping, Zheng Jimin, Jia Zongchao
College of Chemistry, Beijing Normal University, Beijing 100875, China.
School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
iScience. 2021 Jul 22;24(8):102895. doi: 10.1016/j.isci.2021.102895. eCollection 2021 Aug 20.
The mitochondrial uniporter is a Ca-selective ion-conducting channel in the inner mitochondrial membrane that is involved in various cellular processes. The components of this uniporter, including the pore-forming membrane subunit MCU and the modulatory subunits MCUb, EMRE, MICU1, and MICU2, have been identified in recent years. Previously, extensive studies revealed various aspects of uniporter activities and proposed multiple regulatory models of mitochondrial Ca uptake. Recently, the individual auxiliary components of the uniporter and its holocomplex have been structurally characterized, providing the first insight into the component structures and their spatial relationship within the context of the uniporter. Here, we review recent uniporter structural studies in an attempt to establish an architectural framework, elucidating the mechanism that governs mitochondrial Ca uptake and regulation, and to address some apparent controversies. This information could facilitate further characterization of mitochondrial Ca permeation and a better understanding of uniporter-related disease conditions.
线粒体单向转运体是线粒体内膜中一种对钙离子具有选择性的离子传导通道，参与多种细胞过程。近年来，已鉴定出该单向转运体的组成成分，包括形成孔道的膜亚基MCU以及调节亚基MCUb、EMRE、MICU1和MICU2。此前，大量研究揭示了单向转运体活性的多个方面，并提出了多种线粒体钙摄取的调节模型。最近，已对单向转运体及其全复合物的各个辅助成分进行了结构表征，首次深入了解了单向转运体背景下各成分的结构及其空间关系。在此，我们回顾了近期关于单向转运体的结构研究，试图建立一个架构框架，阐明控制线粒体钙摄取和调节的机制，并解决一些明显的争议。这些信息有助于进一步表征线粒体钙渗透，并更好地理解与单向转运体相关的疾病状况。
