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

By B. Kornmann, Erin Currie, Sean R. Collins, M. Schuldiner, J. Nunnari, J. Weissman, P. Walter. Science, 2009

1,248 citations recorded by the source corpus.

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. A protein complex zippers mitochondria to endoplasmic reticulum for phospholipid transfer. 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c6e19556384484d8f723bb06c2023680b9236fc9

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In Molecular Biology

1. T. Langer
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Citations in the corpus

• A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles (2014, background): “A molecular understanding of these contacts has been advanced through studies in yeast and mammalian models (Csordas et al, 1999; de Brito & Scorrano, 2008; Kornmann et al, 2009) and is reviewed elsewhere.”
• Molecular mechanisms and physiological functions of mitophagy (2021, neutral): “In yeast, mitochondria and the ER are connected at contact sites via the ER – mitochondria encounter structure (ERMES) complex that facilitates phospholipid transfer between these two organelles (Kornmann et al , 2009).”
• Lipid map of the mammalian cell (2011, background): “The first protein complexes at ER–mitochondria contact sites have been identified (de Brito and Scorrano, 2008; Kornmann et al., 2009).”
• Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface (2010, neutral): “The tethers show various lengths and seem to include the Mmm1/Mdm10/Mdm12/Mdm34 complex in yeast (Kornmann et al., 2009) and IP3 receptor (IP3R)-containing complexes (Szabadkai et al., 2006), Mfn2 (de Brito and Scorrano, 2008), and several other proteins (Csordás et al., 2006; Merk- wirth and…”
• Making heads or tails of phospholipids in mitochondria (2011, methodology): “One major consequence of this PE export is the synthesis of PC in the ER by the sequential methylation of the primary amine of PE, catalyzed by the yeast methyltransferases Pem1 and Pem2 (originally named Cho2 and Opi3; Kuchler et al., 1986; Kodaki and Yamashita, 1987, 1989).”