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lipidomic/proteomic approach which also revealed several novel putative LP proteins. Finally, LP protein targeting and topology were studied using the squalene epoxidase Erg1p, a typical LP protein, as a model. These studies showed that the majority of the protein faced the cytosol, and only a small part was protected by the membrane. We assume that this may be a general feature of LP proteins. Melanie Connerth: Lipid traffic in the yeast The yeast Saccharomyces cerevisiae is a suitable organism for studies of lipid homeostasis in the cell. Processes involved in the biosynthesis of lipid compounds such as fatty acids, neutral lipids and phospholipids are well understood and located to different subcellular compartments. Two major yeast organelles involved in fatty acid turnover are peroxisomes harboring steps of beta-oxidation and lipid particles (LP) which are the storage organelle for excess fatty acids in the cell. Biogenesis of both compartments is not completely understood yet and little is known about mechanisms of lipid supply to either of these organelles. This Thesis was aimed at elucidation of lipid traffic routes towards and from peroxisomes and LP and the interplay of fatty acid utilization processes in both compartments. Initially, phospholipid supply to peroxisomal membranes was investigated in some detail with focus on phosphatidylethanolamine (PE) transport to peroxisomes. These studies revealed that the four different PE biosynthetic pathways contributed with different efficiency to this process. Moreover, a hybrid of the PE methyltransferase Opi3p was introduced into peroxisomes of an OPI3 deletion mutant which allowed us to measure transport of PE to peroxisomes by appearance of phosphatidylcholine (PC) in peroxisomal membranes. The major take-home message from these experiments was that direct membrane contact most likely accounts for delivery of lipids from their sites of synthesis to peroxisomes. During these studies, a link of peroxisomes with LP, the neutral lipid storage compartment, was also discovered. It was shown that exogenous oleic acid was primarily stored in LP in the form of triacylglycerols (TAG) and subsequently mobilized by a subset of already known as well as novel lipases/hydrolases for supply to peroxisomes. In the course of complete lipidome and proteome analyses of LP a novel and specific inhibitory effect of oleate on the activity of the steryl ester synthase Are2p was discovered thus revealing a new aspect of yeast lipotoxicity. In summary, data from this Thesis showed that distinct pools of fatty acids serving for different cellular processes exist in the cell, and LP play a major role in regulating lipid homeostasis. These data are a step forward in our understanding of cellular lipid traffic which may also be applicable to higher eukaryotic cells such as plants and mammals. International cooperations N. Pfanner, Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Germany I. Hapala, Slovak Academy of Sciences, Institute of Animal Biochemistry and Genetics, Ivanka pri Dunaji, Slovak Republic I. Feussner, Plant Biochemistry, Albrecht-von-Haller-Institute of Plant Sciences, Georg- August University Göttingen, Germany R. Erdmann, Institute of Physiological Chemistry, Ruhr-University Bochum, Germany M. Karas, Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Frankfurt, Germany R. Rajasekharan, Department of Biochemistry, Indian Institute of Science, Bangalore, India 22
Research projects FWF P21429: Phosphatidylserine decarboxylase FWF P18857: Neutral lipid storage and mobilization in the yeast Saccharomyces cerevisiae FWF L-178 (Translational Research): Characterization of organelles from the yeast Pichia pastoris FWF PhD Program: Molecular Enzymology FWF P23029 Lipases of the yeast Saccharomyces cerevisiae Austrian Center of Industrial Biotechnology (ACIB): Pichia pastoris Cell factory and Protein Production Invited Lecture 1. S. Rajakumari, M. Connerth, K. Grillitsch, S. Horvath, R. Rajasekharan and G. Daum Fatty acid channeling from depots to biomembranes in the yeast International Lipid Symposium: Cell Biology and Metabolism, Beijing, China, 1-3 September 2010 Publications 1. Rajakumari, S. and Daum, G. Janus-faced enzymes yeast Tgl3p and Tgl5p catalyze lipase and acyltransferase reactions Mol. Biol. Cell 21 (2010) 501-510 2. Schuiki, I., Schnabl, M., Czabany, T., Hrastnik, C. and Daum, G. Phosphatidylethanolamine synthesized by four different pathways is supplied to the plasma membrane of the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta 1801 (2010) 480-486 3. Spanova, M., Czabany, T., Zellnig, G., Leitner, E., Hapala, I. and Daum, G. Effect of lipid particle biogenesis on the subcellular distribution of squalene in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 285 (2010) 6127-6133 4. Rajakumari, S. and Daum, G. Multiple functions as lipase, steryl ester hydrolase, phospholipase and acyltransferase of Tgl4p from the yeast Saccharomyces cerevisiae. J. Biol. Chem. 285 (2010) 15769-15776 5. Wagner, M., Hoppe, K., Czabany, T., Heilmann, M., Daum, G., Feussner, I. and Fulda, M. Identification and characterization of an acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) gene from the microalga O. tauri. Plant Physiol. Biochem. 48 (2010) 407-416 6. Connerth, M., Czabany, T., Wagner, A., Zellnig, G., Leitner, E., Steyrer, E. and Daum, G. Oleate inhibits steryl ester synthesis and causes liposensitivity in the yeast. J. Biol. Chem. 285 (2010) 26832–26841 7. Rajakumari, S, Rajasekharan, R. and Daum, G. Triacylglycerol lipolysis is linked to sphingolipid and phospholipid metabolism of the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta 1801 (2010) 1314-1322 23
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Page 3 and 4: Brief History of the Institute of B
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