Protein integration into the mitochondrial outer membrane

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Most mitochondrial proteins are encoded by nuclear DNA, synthesized in the cytosol, and imported into the various mitochondrial sub-compartments. Proteins of the outer membrane contain non-cleavable targeting and sorting signals. Currently, these signals and the mechanism of protein integration into the mitochondrial outer membrane are unclear. One goal of the proposed study is to investigate the membrane integration pathway of proteins that span the outer membrane once. To that end, we will combine an insertion assay based on site-specific modification with the usage of lipid vesicles and mitochondria isolated from various strains. Pull-down assays will be used to identify a putative insertase for such proteins. Furthermore, the molecular mechanism by which precursors of ß-barrel proteins are targeted to mitochondria and sorted within the organelle will be studied. To address this questions we will search for targeting signals in these proteins and will analyze the relay of precursor proteins from the TOM to the TOB complex. Furthermore, we will use a genetic screen to study the function of single components of the TOB machinery. These experiments will provide new insights into the biogenesis of mitochondrial outer membrane proteins.