EMRE is an essential component of the mitochondrial calcium uniporter complex.

EMRE is an essential component of the mitochondrial calcium uniporter complex.
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DOI:
10.1126/science.1242993
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发表时间:
2013-12-13
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Mootha VK
Mootha VK
中科院分区:
其他
文献类型:
--
作者:
Sancak Y;Markhard AL;Kitami T;Kovács-Bogdán E;Kamer KJ;Udeshi ND;Carr SA;Chaudhuri D;Clapham DE;Li AA;Calvo SE;Goldberger O;Mootha VK

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线粒体单向转运体是细胞器内膜中的高度选择性钙通道。它的分子组成包括EF-手含有蛋白质线粒体钙摄取1(MICU 1)和MICU 2和孔形成亚基线粒体钙单向转运体(MCU)。我们试图实现一个完整的分子表征的uniporter holocomplex(单重)。定量质谱的亲和纯化的单重回收MICU 1和MICU 2,MCU及其partial MCUB,和基本MCU调节器(EMRE),以前未表征的蛋白质。EMRE是一个10 kD的后生动物特异性蛋白,具有一个单一的跨膜结构域。在它的情况下,单向转运体通道的活动丢失,尽管完整的MCU表达和寡聚化。MCU与MICU 1和MICU 2的交互需要EMRE。因此,EMRE对于体内单向转运体电流是必不可少的,并且还将MICU 1和MICU 2的钙敏感作用与MCU的钙传导作用联系起来。
The mitochondrial uniporter is a highly selective calcium channel in the organelle’s inner membrane. Its molecular components include the EF-hand containing proteins mitochondrial calcium uptake 1 (MICU1) and MICU2 and the pore forming subunit mitochondrial calcium uniporter (MCU). We sought to achieve a full molecular characterization of the uniporter holocomplex (uniplex). Quantitative mass spectrometry of affinity-purified uniplex recovered MICU1 and MICU2, MCU and its paralog MCUb, and essential MCU regulator (EMRE), a previously uncharacterized protein. EMRE is a 10 kD, metazoan specific protein with a single transmembrane domain. In its absence, uniporter channel activity was lost despite intact MCU expression and oligomerization. EMRE was required for the interaction of MCU with MICU1 and MICU2. Hence, EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium conducting role of MCU.
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