Detailseite
Projekt
Role of prohibitins for proteolytic processes within mitochondria
Antragsteller
Professor Dr. Thomas Langer
Fachliche Zuordnung
Stoffwechselphysiologie, Biochemie und Genetik der Mikroorganismen
Förderung
Förderung von 2004 bis 2009
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5422907
Prohibitins comprise a conserved and ubiquitous family of eukaryotic proteins which exhibit sequence similarity to eubacterial HflK and HflC, regulatory proteins of the AAA protease FtsH. Prohibitins are localised to the mitochondrial inner membrane where they form a high molecular mass complex and assemble with the m-AAA protease. We observed an accelerated degradation of inner membrane proteins by the m-AAA protease in yeast mitochondria lacking prohibitins pointing to a regulation of AAA proteases which is conserved from eubacteria to eukaryotes. In the proposed research project, we will characterise the regulatory role of prohibitins during membrane protein degradation. It will be of particular interest to examine whether the prohibitin complex exerts chaperone activity during proteolysis and/or affects the enzymatic activity of the m-AAA protease. We will furthermore characterise the biogenesis of the prohibitin complex and analyse the structural organisation of purified complexes by electron microscopy. Genetic synthetic lethal and suppressor screens aim at the identification of functional interaction partners of prohibitins in mitochondria. These studies should also reveal a potential link between the turnover of mitochondrial inner membrane proteins and diverse cellular functions previously attributed to prohibitins including senescence, cell cycle regulation and cancer, and the maintenance of mitochondrial morphology
DFG-Verfahren
Schwerpunktprogramme
