ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen

• Published in: Science (American Association for the Advancement of Science) Vol. 325; no. 5939; pp. 477 - 481
• Main Authors: Kornmann, Benoît, Currie, Erin, Collins, Sean R, Schuldiner, Maya, Nunnari, Jodi, Weissman, Jonathan S, Walter, Peter
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 24-07-2009; The American Association for the Advancement of Science
• Subjects: Animals; Biological and medical sciences; Biosynthesis; Calcium Signaling - genetics; Cell structures and functions; Cellular biology; Chimeras; Endoplasmic Reticulum - physiology; Eukaryotic cells; Fundamental and applied biological sciences. Psychology; Lipids; Membrane Proteins - metabolism; Mice; Mitochondria; Mitochondria - physiology; Mitochondria and cell respiration; Mitochondrial Proteins - metabolism; Molecular and cellular biology; Molecular biology; Organelles; Phenotypes; Phospholipids; Phospholipids - biosynthesis; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Respiration; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - metabolism; Signal transduction; Cell organelle; Calcium; Phospholipid; Molecular interaction; Biosynthesis; Alkaline earth metal; Complex lipid; Metabolism; Inorganic element; Cell signaling; Mitochondria; Endoplasmic reticulum; Communication
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1175088

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.