Abstract:
Mitochondria are cellular organelles that perform various functions within cells. They are responsible for ATP production, cell-signal regulation, autophagy, and cell apoptosis. Because the mitochondrial proteins that perform these functions need Ca2+ ions for their activity, mitochondria have ion channels to selectively uptake Ca2+ ions from the cytoplasm. The ion channel known to play the most important role in the Ca2+ uptake in mitochondria is the mitochondrial calcium uniporter (MCU) holo-complex located in the inner mitochondrial membrane (IMM). This ion channel complex exists in the form of a complex consisting of the pore-forming protein through which the Ca2+ ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca2+ uptake by the MCU holo-complex. Studies of this MCU holocomplex have long been conducted, but we didn\'t know in detail how mitochondria uptake Ca2+ ions through this ion channel complex or how the activity of this ion channel complex is regulated. Recently, the protein structure of the MCU holo-complex was identified, enabling the mechanism of Ca2+ uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of action of the MCU holo-complex at the molecular level based on the Cryo-EM structure of the MCU holo-complex to help understand how mitochondria uptake the necessary Ca2+ ions through the MCU holo-complex and how these Ca2+ uptake mechanisms are regulated. [BMB Reports 2022; 55(11): 528-534].
摘要:
线粒体是在细胞内执行各种功能的细胞器。他们负责ATP的生产,细胞信号调节,自噬,和细胞凋亡。因为执行这些功能的线粒体蛋白质需要Ca2+离子来进行活动,线粒体具有离子通道以从细胞质中选择性地摄取Ca2离子。已知在线粒体中的Ca2摄取中起最重要作用的离子通道是位于线粒体内膜(IMM)的线粒体钙单蛋白(MCU)完整复合物。这种离子通道复合物以由成孔蛋白组成的复合物形式存在,Ca2+离子通过该复合物被转运到线粒体基质中,以及参与调节MCU全复合物摄取Ca2活性的辅助蛋白。这种MCU整体复合体的研究已经进行了很长时间,但是我们不知道线粒体是如何通过这种离子通道复合物摄取钙离子的,也不知道这种离子通道复合物的活性是如何调节的。最近,确定了MCU完整复合物的蛋白质结构,能够证实Ca2+的摄取机制及其通过MCU全复合物的调节。在这次审查中,我将根据MCU全息复合物的Cryo-EM结构在分子水平上介绍MCU全息复合物的作用机理,以帮助了解线粒体如何通过MCU全息复合物吸收必要的Ca2离子以及如何调节这些Ca2吸收机制。[BMB报告2022;55(11):528-534]。