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EMRE Is an Essential Component of the Mitochondrial Calcium Uniporter Complex

机译：EMRE是线粒体钙Uniporter复合体的重要组成部分

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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 AACU 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.
机译：线粒体单向转运蛋白是细胞器内膜中高度选择性的钙通道。它的分子成分包括含EF手的钙结合蛋白线粒体钙摄取1（MICU1）和MICU2，以及成孔亚基线粒体钙单向转运蛋白（MCU）。我们试图实现单端口全络合物（uniplex）的完整分子表征。亲和纯化的单链体回收的MICU1和MICU2，MCU及其类似物MCUb和必需的AACU调节剂（EMRE）（一种以前未表征的蛋白）的定量质谱分析。 EMRE是一种具有单个跨膜结构域的10公斤，后生动物特异性蛋白。在缺少它的情况下，尽管完整的MCU表达和寡聚化，单通道通道的活性仍然丧失。 MCU与MICU1和MICU2的交互需要EMRE。因此，EMRE对于体内单向电流是必不可少的，并且另外将MICU1和MICU2的钙敏感作用与MCU的钙传导作用联系在一起。

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  • 来源
    《Science》 |2013年第6164期|1379-1382|共4页
  • 作者

    Yasemin Sancak; Andrew L. Markhard; Toshimori Kitami; Erika Kovacs-Bogdan; 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;

  • 作者单位

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA,RCAI, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA;

    Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA;

    Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA;

    Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA, USA,Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA;

    Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA, USA;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA;

    Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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