Prof. Dr. Nikolaus Pfanner (CIBSS PI), Institute of Biochemistry and Molecular Biology, University of Freiburg
Prof. Dr. Nils Wiedemann (CIBSS AI), Institute of Biochemistry and Molecular Biology, University of Freiburg
Mitochondria play central roles in bioenergetics and cellular metabolism. They are dynamic organelles and are involved in key steps of quality control and apoptosis regulation. The biogenesis of mitochondria requires the coordination of two genomes (nuclear and mitochondrial) and the signal-directed import of about 1,000 different proteins from the cytosol into mitochondria, followed by their sorting into the four mitochondrial subcompartments and assembly into oligomeric complexes. We discovered that the mitochondrial protein import machineries do not function as independent units, but are functionally and physically connected with machineries of quite diverse functions, including metabolite transport, respiratory complexes, mitochondrial membrane morphology and lipid biosynthesis. Under different metabolic conditions, mitochondria undergo a re-arrangement of their protein complement and membrane organization. We will study the molecular and functional organization of the membrane-spanning mitochondrial organizing network and its remodelling during metabolic shift from fermentation to respiration in collaboration with Sabine Rospert and Heike Rampelt. The project will address molecular mechanisms of signal-directed preprotein transfer from the cytosol to import, assembly and quality control in the mitochondrial inner membrane, and the role of the mitochondrial contact site and cristae organizing system MICOS as regulatory hub.