The PTS1-receptor of Saccharomyces cerevisiae (PAS10p) and its interacting partners

Peroxisomes are an essential metabolic compartment in eukaryotic cells, involved in degradation of fatty acids, biosynthesis of cholesterol, and other metabolic pathways. Inherited lack of their function is correlated with human diseases like Zellweger syndrome or adrenoleukodystrophy. All proteins found in the peroxisomal matrix have to be imported from the cytoplasm, but the mechanism of this process is not well understood. Each peroxisomal protein carries a targeting signal recognized by a receptor, in this case the Pex5-protein (formerly Pas10-protein), which in turn carries the protein to the surface of the organelle, where a proteinaceous complex permits the translocation across the membrane. Using yeast as a model system experiments carried out during this project led to the identification of one of the components of the import machinery, the Pex14-protein, and to the characterization of its numerous interaction partners. Furthermore, the interaction between the receptor Pex5p and the targeting signal was studied in detail. Receptors from different organisms show subtle differences in recognition of these targeting signals, which may explain, why some proteins are imported into peroxisomes in one organism but not in another. In addition, two enzymes responsible for the breakdown of unsaturated fatty acids in yeast were identified and localized to peroxisomes. Last but not least, preliminary experiments to set up an in vitro-import system into peroxisomes from yeast cells were carried out. Only such an in vitro-system will permit a full understanding of the mechanism involved, which finally may lead to therapy.