An ER-mitochondria tethering complex revealed by a synthetic biology screen.

An ER-mitochondria tethering complex revealed by a synthetic biology screen.
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DOI:
10.1126/science.1175088
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发表时间:
2009-07-24
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Walter P
Walter P
中科院分区:
其他
文献类型:
--
作者:
Kornmann B;Currie E;Collins SR;Schuldiner M;Nunnari J;Weissman JS;Walter P

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细胞器之间的通讯是所有真核细胞的重要特征。为了揭示参与线粒体/内质网(ER)连接的成分,我们筛选了可以通过人工连接两个细胞器的合成蛋白质补充的突变体。我们鉴定了Mmm 1/Mdm 10/Mdm 12/Mdm 34复合物作为ER和线粒体之间的分子系链。栓系复合物由ER和线粒体的蛋白质组成。利用全基因组遗传相互作用图谱,我们发现,拴系复合物的组件功能连接到磷脂生物合成和钙信号基因。在突变细胞中,磷脂生物合成受损。拴系复合物定位于离散的焦点,这表明ER和线粒体之间的紧密并列的离散网站促进细胞器间的钙和磷脂交换。
Communication between organelles is an important feature of all eukaryotic cells. To uncover components involved in mitochondria/endoplasmic reticulum (ER) junctions, we screened for mutants that could be complemented by a synthetic protein designed to artificially tether the two organelles. We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. The tethering complex was composed of proteins resident of both ER and mitochondria. With the use of genome-wide mapping of genetic interactions, we showed that the components of the tethering complex were functionally connected to phospholipid biosynthesis and calcium-signaling genes. In mutant cells, phospholipid biosynthesis was impaired. The tethering complex localized to discrete foci, suggesting that discrete sites of close apposition between ER and mitochondria facilitate interorganelle calcium and phospholipid exchange.
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