Henan Key Laboratory of Medical Tissue Regeneration, College of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
Henan Key Laboratory of Neurorestoratology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Br J Pharmacol. 2019 May;176(9):1190-1205. doi: 10.1111/bph.14632. Epub 2019 Apr 3.
Due to its Ca buffering capacity, the mitochondrion is one of the most important intracellular organelles in regulating Ca dynamic oscillation. Mitochondrial calcium uniporter (MCU) is the primary mediator of Ca influx into mitochondria, manipulating cell energy metabolism, ROS production, and programmed cell death, all of which are critical for carcinogenesis. The understanding of the uniporter complex was significantly boosted by recent groundbreaking discoveries that identified the uniporter pore-forming subunit MCU and its regulatory molecules, including MCU-dominant negative β subunit (MCUb), essential MCU regulator (EMRE), MCU regulator 1 (MCUR1), mitochondrial calcium uptake (MICU) 1, MICU2, and MICU3. These provide the means and molecular platform to investigate MCU complex (uniplex)-mediated impaired Ca signalling in physiology and pathology. This review aims to summarize the progress of the understanding regulatory mechanisms of uniplex, roles of uniplex-mediated Ca signalling in cancer, and potential pharmacological inhibitors of MCU.
由于其钙缓冲能力，线粒体是调节钙动态振荡的最重要的细胞内细胞器之一。线粒体钙单向转运蛋白 (MCU) 是钙流入线粒体的主要介质，调节细胞能量代谢、ROS 产生和程序性细胞死亡，所有这些对致癌作用都至关重要。最近的突破性发现极大地推动了对单向转运蛋白复合物的理解，这些发现确定了单向转运蛋白的孔形成亚基 MCU 及其调节分子，包括 MCU 显性负 β 亚基 (MCUb)、必需 MCU 调节剂 (EMRE)、MCU 调节剂 1 (MCUR1)、线粒体钙摄取 (MICU)1、MICU2 和 MICU3。这些为研究 MCU 复合物 (单向转运蛋白) 介导的生理和病理钙信号受损提供了手段和分子平台。本综述旨在总结单向转运蛋白调节机制的研究进展、单向转运蛋白介导的 Ca 信号在癌症中的作用以及 MCU 的潜在药理学抑制剂。
