Phosphatidylethanolamine of yeast mitochondria

Mitochondria are important organelles containing enzymes of respiration, energy production and various other metabolic processes. Whereas our knowledge about protein import and assembly into mitochondria increased enormously during studies of the last twenty years, little is known about the role of lipids in the biogenesis, function and maintenance of the integrity of this organelle. Recent research, however, has clearly demonstrated the increasing awareness of the importance of lipids in various cellular processes including formation of mitochondria. Our laboratory uses the yeast Saccharomyces cerevisiae, which has become a valuable and reliable model system for cell biology, to address these problems. The project presented here is aimed at the identification of novel components which contribute to lipid homeostasis and govern the assembly of lipids in mitochondrial membranes with special emphasis on the role of phosphatidyl-ethanolamine in mitochondrial and cellular function. Studies concerning the role of phosphatidylethanolamine as a key lipid of yeast mitochondria were initiated in our laboratory during the preceding FWF project 14468. Genetic screenings with overlapping strategies were designed to detect mutations which cause defects in the incorporation of phosphatidylethanolamine into mitochondrial membranes. These investigations demonstrated for the first time that phosphatidylethanolamine is indispensable for mitochondrial function. In the project proposed here these studies will be completed and continued. Moreover, new screenings employing DNA microarray technology and yeast proteome analysis will be performed. Based on previous, ongoing and newly proposed screenings, a systematic strategy to identify and characterize components involved in the homeostasis of lipids in mitochondria will be employed making use of molecular biological, cell biological and biochemical methods with increasing specificity. Yeast mutants identified in screenings will be subjected to phenotypic and biochemical analysis, and the respective genes will be identified. Strains with abnormal mitochondrial lipid pattern will be characterized in detail, especially with respect to mitochondrial function and morphology, and synthesis and intracellular translocation of lipids. Individual studies of mutants and gene products will clarify the biochemical and cell biological function of the proteins identified, provide a deeper insight into the network of processes related to lipid assembly into mitochondria, and contribute to our general understanding of the role of lipids in mitochondria.

Mitochondria are important organelles containing enzymes of respiration, energy production and various other metabolic processes. Whereas our knowledge about protein import and assembly into mitochondria increased enormously during studies of the last twenty years, little is known about the role of lipids in the biogenesis, function and maintenance of the integrity of this organelle. Recent research, however, has clearly demonstrated the increasing awareness of the importance of lipids in various cellular processes including formation of mitochondria. Our laboratory uses the yeast Saccharomyces cerevisiae, which has become a valuable and reliable model system for cell biology, to address these problems. The project presented here is aimed at the identification of novel components which contribute to lipid homeostasis and govern the assembly of lipids in mitochondrial membranes with special emphasis on the role of phosphatidyl-ethanolamine in mitochondrial and cellular function. Studies concerning the role of phosphatidylethanolamine as a key lipid of yeast mitochondria were initiated in our laboratory during the preceding FWF project 14468. Genetic screenings with overlapping strategies were designed to detect mutations which cause defects in the incorporation of phosphatidylethanolamine into mitochondrial membranes. These investigations demonstrated for the first time that phosphatidylethanolamine is indispensable for mitochondrial function. In the project proposed here these studies will be completed and continued. Moreover, new screenings employing DNA microarray technology and yeast proteome analysis will be performed. Based on previous, ongoing and newly proposed screenings, a systematic strategy to identify and characterize components involved in the homeostasis of lipids in mitochondria will be employed making use of molecular biological, cell biological and biochemical methods with increasing specificity. Yeast mutants identified in screenings will be subjected to phenotypic and biochemical analysis, and the respective genes will be identified. Strains with abnormal mitochondrial lipid pattern will be characterized in detail, especially with respect to mitochondrial function and morphology, and synthesis and intracellular translocation of lipids. Individual studies of mutants and gene products will clarify the biochemical and cell biological function of the proteins identified, provide a deeper insight into the network of processes related to lipid assembly into mitochondria, and contribute to our general understanding of the role of lipids in mitochondria.