EMRE Is an Essential Component of the Mitochondrial Calcium Uniporter Complex

被引：556

作者：

Sancak, Yasemin ^{[1
,2
]}

Markhard, Andrew L. ^{[1
]}

Kitami, Toshimori ^{[1
,2
]}

Kovacs-Bogdan, Erika ^{[1
]}

Kamer, Kimberli J. ^{[1
]}

Udeshi, Namrata D. ^{[2
]}

Carr, Steven A. ^{[2
]}

Chaudhuri, Dipayan ^{[3
,4
,5
]}

Clapham, David E. ^{[3
,4
]}

Li, Andrew A. ^{[1
]}

Calvo, Sarah E. ^{[1
,2
]}

Goldberger, Olga ^{[1
]}

Mootha, Vamsi K. ^{[1
,2
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Syst Biol, Boston, MA 02115 USA

[2] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA

[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Cardiol,Childrens Hosp, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[5] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

来源：

SCIENCE | 2013年 / 342卷 / 6164期

关键词：

CA2+ UPTAKE; PROTEIN; MICU1; MCU;

D O I：

10.1126/science.1242993

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The mitochondrial uniporter is a highly selective calcium channel in the organelle's inner membrane. Its molecular components include the EF-hand-containing calcium-binding 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-kilodalton, 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.

引用

页码：1379 / 1382

页数：4

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