Emergence of repurposed drugs as modulators of MCU channel for clinical therapeutics.
Emergence of repurposed drugs as modulators of MCU channel for clinical therapeutics.
复制标题
重新利用药物作为临床治疗的 MCU 通道调节剂的出现。
DOI：
10.1016/j.ceca.2021.102456
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发表时间：
2021
期刊：
影响因子：
4
通讯作者：
Madesh,Muniswamy
中科院分区：
文献类型：
--
作者：
Vishnu,Neelanjan;Wilson,Justin;Madesh,Muniswamy
线粒体Ca 2+摄取由高选择性通道线粒体钙单向转运体（MCU）介导[1-4]，并响应于各种生理刺激而发生，这些刺激通常由内质网释放Ca 2+触发。MCU复合物的核心组分包括成孔亚基（即MCU和必需MCU调节剂[EMRE]）和调节蛋白（即MCUb、MCUR 1、MICU 1、MICU 2、MICU 3、LETM 1和SLC 25 A23）。几项研究已经阐明了MCU单独和与EMRE组合的结构[4]，揭示了与EMRE具有1：1化学计量的四聚体结构。MCU复杂成分的遗传变异与几种疾病的发展有关，表明该通道在生物体生理学中起着重要作用。例如，MCU过表达与肺癌、胃癌和肝癌的进展相关。本手稿在Elsevier用户许可证https：//www下提供。爱思唯尔。com/open-access/userlicense/1.0/
Mitochondrial Ca2+ uptake is mediated by the highly selective channel, the mitochondrial calcium uniporter (MCU)[1-4] and occurs in response to various physiological stimuli, which are often triggered by the release of Ca2+ from the endoplasmic reticulum. The core components of the MCU complex include pore-forming subunits (ie, MCU, and Essential MCU Regulator [EMRE]) and regulatory proteins (ie, MCUb, MCUR1, MICU1, MICU2, MICU3, LETM1, and SLC25A23). Several studies have elucidated the structure of the MCU alone and in combination with EMRE [4], revealing tetrameric structure with 1: 1 stoichiometry with EMRE. Genetic variants of the MCU complex components have been linked to the development of several diseases, suggesting that this channel plays an important role in organismal physiology. For example, MCU overexpression is associated with the progression of lung, gastric, and liver cancers.© 2021 published by Elsevier. This manuscript is made available under the Elsevier user license https://www. elsevier. com/open-access/userlicense/1.0/