An integrative stress response network activated by mitochondrial membrane signalling assemblies

Prof. Dr. Bettina Warscheid (CIBSS-PI), Institute of Biology II - Functional Proteomics (Faculty of Biology), University of Freiburg

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Mitochondria are highly dynamic organelles which execute a large variety of functions ranging from energy metabolism with respiration and synthesis of ATP to lipid, amino acid, iron and oxygen metabolism. To fulfil this array of functions, mitochondria harbor a large set of proteins with an estimated number of 1,000 proteins in yeast and 1,500 proteins in human cells. However, 99% of all mitochondrial proteins are nuclear-encoded. Thus, biogenesis and maintenance of the mitochondrial proteome largely depend on the import of mitochondrial preproteins synthesized on cytosolic ribosomes. We recently discovered that slowdown in mitochondrial protein import activates distinct cellular responses at a post-transcriptional level. We will analyse the cellular stress response signalling network activated by dysfunction of mitochondrial membrane assemblies central for protein import. Vice versa, we will investigate which and how stress response signalling pathways converge on mitochondrial membrane signalling assemblies to counteract mitochondrial dysfunction. Our research will contribute to a detailed understanding of how mitochondria function as integrative signalling hubs for connecting cell metabolism with intracellular signalling and epigenetic control in eukaryotic cells (CIBSS CST Mito-Hub).