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

线粒体是几乎所有真核生物的重要细胞器。它们的形状是高度动态的，取决于连续的聚变和裂变事件。线粒体动力学与真核病原体的生存能力、致病性和胁迫耐受性的相关性迄今尚未被探索。因此，本研究计划旨在从分子水平上研究机会致病性霉菌烟曲霉的线粒体分裂和融合。通过构建和表征相关基因的突变株，将探索这些机制对于致病性和抗真菌化合物（例如由免疫细胞和抗真菌药物释放的化合物）的抗性的重要性。此外，将分析某些抗真菌化合物的活性和特异性，推测其对线粒体动力学的影响。该项目将有助于解剖哺乳动物和真菌线粒体分裂和融合之间的差异，从而确定各自的机制是否适合作为抗真菌靶结构。

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.