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

Science  24 Jul 2009:
Vol. 325, Issue 5939, pp. 477-481
DOI: 10.1126/science.1175088

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Making Connections

Endoplasmic reticulum (ER)–mitochondria connections have been implicated in many physiological processes, including calcium homeostasis, signaling, membrane biogenesis, and apoptosis. Kornmann et al. (p. 477, published online 25 June; see the Perspective by Wiedemann et al.) looked for a proteinaceous link between the ER and mitochondria and, using combinations of synthetic biology and classical yeast genetics, found a protein complex that tethers the two organelles. A large-scale genetic interaction map suggests that these ER-mitochondria connections are important for interorganellar phospholipid exchange.

Abstract

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.

  • Present address: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.

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

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