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Functional characterization of mitochondrial AAA proteases in Saccharomyces cerevisiae
Antragsteller
Professor Dr. Thomas Langer
Fachliche Zuordnung
Stoffwechselphysiologie, Biochemie und Genetik der Mikroorganismen
Förderung
Förderung von 2002 bis 2005
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5360024
AAA proteases are a conserved class of membrane-bound ATP-dependent proteases that are ubiquitously present in mitochondria and chloroplasts of eukaryotic cells. In the proposed research project, the function of two AAA proteases in mitochondria of the yeast Saccharomyces cerevisiae will be studied. Both proteases form a membrane-integrated quality control system whose activity is essential for mitochondrial biogenesis and cell growth. We will examine mechanisms guiding the turnover of polytopic membrane proteins by these proteases. It will be of particular interest to understand how substrate polypeptides are recognized and bound by AAA proteases and subsequently dislocated from the membrane bilayer for proteolysis. Another major focus of our studies will be the identification of endogenous substrates of AAA proteases in mitochondria. A genetic and a proteomic approach will be used to identify and characterize short-lived mitochondrial proteins with potential regulatory functions during organellar biogenesis. These studies should not only further our understanding of the pleiotropic defects associated with AAA protease mutations in yeast, but should also provide new insights into the pathogenesis of a neurodegenerative disorder caused by an inactivation of an AAA protease in humans.
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