Mitochondria are the powerhouse of eukaryotic cells and produce the bulk of cellular ATP through oxidative phophorylation. Moreover, mitochondria fulfil additional important cellular tasks such as the generation of FeS-clusters, they are involved in amino acid and lipid metabolism, and the regulation of programmed cell death.
Most of the approximately 1000 mitochondrial proteins are imported from the cytosol into mitochondria post-translationally. However, a small number of hydrophobic proteins are synthesized within mitochondria.
We are interested in understanding the molecular mechanisms by which proteins are transported across the mitochondrial membranes and to find out how multi-protein complexes in the inner membrane (TIM complexes; translocation machineries of the inner membrane) mediate this task. In another aspect of our work we addresses the question as to how newly imported proteins assemble into multi-protein complexes in the inner membrane. In case of the respiratory chain complexes the assembly process is especially demanding since central subunits of the complexes are made within mitochondria. Dedicated chaperone-like factors are required to assist and regulate the assembly process. The analysis of the principles of the biogenesis process and the activities of the assembly factors is of central importance for our understanding of the molecular basis of human mitochondrial disorders. In our work we combine biochemical and genetic techniques on the model organism Saccharomyces cerevisae with experiments in human cell lines. Research topics that we currently address are:
Transport and membrane insertion of mitochondrial proteins.
Assembly of inner mitochondrial membrane complexes and how this process is affected in mitochondrial disorders.
Biogenesis of mitochondrially-encoded proteins.