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Originally published in Science Express on 25 June 2009
Science 24 July 2009:
Vol. 325. no. 5939, pp. 477 - 481
DOI: 10.1126/science.1175088
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Reports

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

Benoît Kornmann,1,* Erin Currie,1,{dagger} Sean R. Collins,2,3,{ddagger} Maya Schuldiner,4 Jodi Nunnari,5 Jonathan S. Weissman,2,3 Peter Walter1,3

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.

1 Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94158, USA.
2 Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
3 Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94158, USA.
4 Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
5 Molecular and Cellular Biology, University of California at Davis, Davis, CA 95616, USA.

{dagger} Present address: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.

{ddagger} Present address: Chemical and Systems Biology, Bio-X Program, Stanford University, Stanford, CA 94305, USA.

* To whom correspondence should be addressed. E-mail: benoit.kornmann{at}ucsf.edu

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