Science：科學(xué)家發(fā)現(xiàn)鈣通道“線粒體蛋白EMRE”

       美國(guó)馬薩諸塞州總醫(yī)院和哈佛醫(yī)學(xué)院等機(jī)構(gòu)組成的研究組zui近發(fā)現(xiàn)鈣運(yùn)輸鏈中的zui后一環(huán)：一個(gè)叫做EMRE的線粒體蛋白。這一研究發(fā)現(xiàn)不僅有望更深入地闡明線粒體的運(yùn)作機(jī)制，還為調(diào)查鈣運(yùn)輸對(duì)于疾病的貢獻(xiàn)——其中包括在生命的頭幾個(gè)月內(nèi)導(dǎo)致死亡的罕見(jiàn)線粒體疾病開(kāi)啟了大門。相關(guān)文章在《Science》雜志上發(fā)表。

原文摘要：

EMRE is an Essential Component of the Mitochondrial Calcium Uniporter Complex

Yasemin Sancak, Andrew L. Markhard, Toshi Kitami, Erika Kovács-Bogdán, Kimberli J. Kamer,Namrata D. Udeshi, Steven A. Carr, Dipayan Chaudhuri, David E. Clapham, Andrew A. Li, Sarah E. Calvo,Olga Goldberger, Vamsi K. Mootha

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.