An ER-mitochondria tethering complex revealed by a synthetic biology screen.
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.
Kornmann
Benoît
B
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94158, USA. benoit.kornmann@ucsf.edu
Currie
Erin
E
Collins
Sean R
SR
Schuldiner
Maya
M
Nunnari
Jodi
J
Weissman
Jonathan S
JS
Walter
Peter
P
D000818:Animals; D020013:Calcium Signaling / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
C089419:MDM10 protein, S cerevisiae; C089418:MMM1 protein, S cerevisiae; C543343:Mdm12 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C543344:mdm34 protein, S cerevisiae