cell20121026-18

来自美国坦普尔大学生物化学系的Muniswamy Madesh实验室发现MICU1是MCU介导的Ca2+ m吸收的“看门人”,而Ca2+适当吸收对于防止[Ca2+]m过载和相关的压力具有重要作用,本篇文章刊登在最新一期《CELL》杂志上。

-2012年10月26日《细胞》


中文翻译


【题目】MICU1是MCU介导的线粒体Ca2+吸收的重要“看门人”

【译文】线粒体对Ca2+的吸收受到一种被叫做单输送体的内膜Ca2+通道的调节。Ca2+的吸收受到内膜(ΔΨm)的适当电压的驱动,这种电压差依赖于质子泵和呼吸链。线粒体基质中Ca2+浓度低于平衡水平的五至六个数量级,但是此现象的形成机制尚且研究的不清楚。我们发现在一般情况下,线粒体蛋白MICU1是维持基质内[Ca2+]m浓度所必须的。在这种蛋白缺乏的情况下,线粒体持续的吸收Ca2+,这引起过度活性氧簇并对凋亡应激反应更加敏感。MICU1与单输送体的孔形成亚基MCU相互作用并且设定Ca2+的阈值为不影响受到MCU介导的Ca2+ m吸收的动力学性质。因此,MICU1是MCU介导的Ca2+ m吸收的“看门人”,而Ca2+适当吸收对于防止[Ca2+]m过载和相关的压力具有重要作用。

英文原稿


[Title]MICU1 Is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake that Regulates Cell Survival

[Authors]Karthik Mallilankaraman, Patrick Doonan, César Cárdenas, Harish C. Chandramoorthy, Marioly Müller, Russell Miller, Nicholas E. Hoffman, Rajesh Kumar Gandhirajan, Jordi Molgó, Morris J. Birnbaum, Brad S. Rothberg, Don-On Daniel Mak, J. Kevin Foskett, Muniswamy Madesh

[Abstract]Mitochondrial Ca2+ (Ca2+m) uptake is mediated by an inner membrane Ca2+ channel called the uniporter. Ca2+ uptake is driven by the considerable voltage present across the inner membrane (ΔΨm) generated by proton pumping by the respiratory chain. Mitochondrial matrix Ca2+ concentration is maintained five to six orders of magnitude lower than its equilibrium level, but the molecular mechanisms for how this is achieved are not clear. Here, we demonstrate that the mitochondrial protein MICU1 is required to preserve normal [Ca2+]m under basal conditions. In its absence, mitochondria become constitutively loaded with Ca2+, triggering excessive reactive oxygen species generation and sensitivity to apoptotic stress. MICU1 interacts with the uniporter pore-forming subunit MCU and sets a Ca2+ threshold for Ca2+m uptake without affecting the kinetic properties of MCU-mediated Ca2+ uptake. Thus, MICU1 is a gatekeeper of MCU-mediated Ca2+m uptake that is essential to prevent [Ca2+]m overload and associated stress.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01225-1

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