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.

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

Phospholipids play multiple roles in cells by establishing the permeability barrier for cells and cell organelles, by providing the matrix for the assembly and function of a wide variety of catalytic processes, by acting as donors in the synthesis of macromolecules, and by actively influencing the functional properties of membrane-associated processes. The function, at the molecular level, of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin in specific cellular processes is reviewed, with a focus on the results of combined molecular genetic and biochemical studies in Escherichia coli. These results are compared with primarily biochemical data supporting similar functions for these phospholipids in eukaryotic organisms. The wide range of processes in which specific involvement of phospholipids has been documented explains the need for diversity in phospholipid structure and why there are so many membrane lipids.

MOLECULAR BASIS FOR MEMBRANE PHOSPHOLIPID DIVERSITY: Why Are There So Many Lipids?

The biosynthesis and functional role of cardiolipin.

Cardiolipin stabilizes respiratory chain supercomplexes.

Lipids of mitochondria.

The PEL1 Gene (Renamed PGS1) Encodes the Phosphatidylglycero-phosphate Synthase ofSaccharomyces cerevisiae

Isolation and Characterization of the Gene (CLS1) Encoding Cardiolipin Synthase in Saccharomyces cerevisiae

Cloning of a gene (PSD1) encoding phosphatidylserine decarboxylase from Saccharomyces cerevisiae by complementation of an Escherichia coli mutant.

Isolation of a chinese hamster ovary (CHO) cDNA encoding phosphatidylglycerophosphate (PGP) synthase, expression of which corrects the mitochondrial abnormalities of a PGP synthase-defective mutant of CHO-K1 cells.

Shao Chun Chang

Papers

The PEL1 Gene (Renamed PGS1) Encodes the Phosphatidylglycero-phosphate Synthase ofSaccharomyces cerevisiae

Isolation and Characterization of the Gene (CLS1) Encoding Cardiolipin Synthase in Saccharomyces cerevisiae

Cloning of a gene (PSD1) encoding phosphatidylserine decarboxylase from Saccharomyces cerevisiae by complementation of an Escherichia coli mutant.

Isolation of a chinese hamster ovary (CHO) cDNA encoding phosphatidylglycerophosphate (PGP) synthase, expression of which corrects the mitochondrial abnormalities of a PGP synthase-defective mutant of CHO-K1 cells.