An ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen

被引:962
作者
Kornmann, Benoit [1 ]
Currie, Erin [1 ]
Collins, Sean R. [2 ,3 ]
Schuldiner, Maya [5 ]
Nunnari, Jodi [4 ]
Weissman, Jonathan S. [2 ,3 ]
Walter, Peter [1 ,3 ]
机构
[1] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
[2] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA
[3] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA
[4] Univ Calif Davis, Davis, CA 95616 USA
[5] Weizmann Inst Sci, IL-76100 Rehovot, Israel
基金
瑞士国家科学基金会;
关键词
ENDOPLASMIC-RETICULUM; SACCHAROMYCES-CEREVISIAE; BIOSYNTHETIC PATHWAYS; YEAST; PHOSPHATIDYLETHANOLAMINE; CARDIOLIPIN; PROTEINS; PHOSPHATIDYLSERINE; INHERITANCE; MORPHOLOGY;
D O I
10.1126/science.1175088
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
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:477 / 481
页数:5
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