MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival.
MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival.
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DOI：
10.1016/j.cell.2012.10.011
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发表时间：
2012-10-26
期刊：
影响因子：
64.5
通讯作者：
Madesh M
中科院分区：
文献类型：
--
作者：
Mallilankaraman K;Doonan P;Cárdenas C;Chandramoorthy HC;Müller M;Miller R;Hoffman NE;Gandhirajan RK;Molgó J;Birnbaum MJ;Rothberg BS;Mak DO;Foskett JK;Madesh M
线粒体Ca 2+（Ca 2 +m）摄取由称为单向转运体的内膜Ca 2+通道介导。Ca 2+摄取是由呼吸链质子泵送产生的跨内膜的相当大的电压（Δ μ m）驱动的。线粒体基质Ca 2+浓度维持在比其平衡水平低5-6个数量级，但如何实现这一点的分子机制尚不清楚。在这里，我们表明，线粒体蛋白MICU 1是需要保持正常的[Ca 2 +]m在基础条件下。在它的情况下，线粒体成为组成性负载Ca 2+，引发过量的活性氧产生和敏感性凋亡应激。MICU 1与单向转运体孔形成亚基MCU相互作用，并为Ca 2 +m摄取设定Ca 2+阈值，而不影响MCU介导的Ca 2+摄取的动力学性质。因此，MICU 1是MCU介导的Ca 2 +m摄取的守门人，这对于防止[Ca 2 +]m过载和相关应激至关重要。
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 5–6 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.
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影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK
内膜的四十千克蛋白是线粒体钙Uniporter。
影响因子：
64.8
作者：
De Stefani, Diego;Raffaello, Anna;Teardo, Enrico;Szabo, Ildiko;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario
影响因子：
4.8
作者：
Filippin, L;Magalhaes, PJ;Pozzan, T
通讯作者：
Pozzan, T
影响因子：
4.1
作者：
CARAFOLI, E;LEHNINGE.AL
通讯作者：
LEHNINGE.AL
影响因子：
16.2
作者：
Herrington, J;Park, YB;Hille, B
通讯作者：
Hille, B