Molecular characterization of mitochondrial fission and fusion mechanisms in Aspergillus fumigatus and their role in pathogenicity, viability and stress tolerance.

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Mitochondria are essential organelles in almost all eukaryotes. Their shape is highly dynamic and depends on continuous fusion and fission events. The relevance of mitochondrial dynamics for the viability, pathogenicity and stress tolerance of eukaryotic pathogens has not been explored so far. This research proposal therefore aims on studying mitochondrial fission and fusion in the opportunistic pathogenic mold Aspergillus fumigatus on a molecular level. By constructing and characterizing mutant strains of relevant genes, the importance of these mechanisms for the pathogenicity and resistance to antifungal compounds, such as those released by immune cells and antimycotic drugs, will be explored. In addition, the activity and specificity of certain antifungal compounds with presumed effects on mitochondrial dynamics will be analyzed. This project will help to dissect the differences between mammalian and fungal mitochondrial fission and fusion and as a result determine whether the respective machineries are suitable as antifungal target structure.