Molecular, cellular and organismal functions of the mitochondrial fusion machinery in animal development

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Mitochondria are cellular organelles whose function is critical for cellular and organismal life throughout all eukaryotic kingdoms. Mitochondria are also highly dynamic organelles that often fuse and divide. However, to date, the functional relevance of mitochondrial dynamics is not well understood. Goal of the proposed studies is to systematically analyze the role of mitochondrial dynamics in the context of animal development. To that end, we are taking advantage of the nematode Caenorhabditis elegans, which due to its highly reproducible development is particularly amenable to studies on animal development. We have begun to analyze the development of C. elegans mutants defective in mitochondrial fusion at single cell resolution. Preliminary results suggest that these mutants exhibit defective differentiation in specific cell lineages, such as a muscle cell lineage (the D lineage). In addition, the mitochondrial unfolded protein response (UPRmt), which couples changes in the protein-folding environment in mitochondria to the expression of nuclear genes, is activated. Using a combination of cell biological, genetic and molecular approaches as well as mass-spectrometry based proteomics, we will study these two responses mechanistically and define the molecular pathways through which they are mediated.