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

烟曲霉线粒体裂变和融合机制的分子特征及其在致病性、活力和胁迫耐受性中的作用。

• 批准号: 249764016
• 负责人: Dr. Johannes Wagener
• 金额: --
• 依托单位: School of Medicine
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/249764016?language=en
• 关键词: Molecular; characterization; mitochondrial; fission; fusion

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.

线粒体是几乎所有真核生物中必需的细胞器。它们的形状是高度动态的，取决于持续的聚变和裂变事件。迄今为止，线粒体动力学与真核病原体的生存力、致病性和胁迫耐受性的相关性尚未被探索。因此，本研究计划旨在从分子水平研究机会性致病霉菌烟曲霉中的线粒体裂变和融合。通过构建和表征相关基因的突变株，将探讨这些机制对于抗真菌化合物（例如免疫细胞和抗真菌药物释放的化合物）的致病性和耐药性的重要性。此外，还将分析某些可能对线粒体动力学有影响的抗真菌化合物的活性和特异性。该项目将有助于剖析哺乳动物和真菌线粒体裂变和融合之间的差异，从而确定各自的机制是否适合作为抗真菌靶结构。

项目成果

Mitochondrial dynamics in the pathogenic mold Aspergillus fumigatus: therapeutic and evolutionary implications

• DOI: 10.1111/mmi.13167
• 发表时间: 2015-12-01
• 期刊: MOLECULAR MICROBIOLOGY
• 影响因子: 3.6
• 作者: Neubauer, Michael;Zhu, Zhaojun;Wagener, Johannes
• 通讯作者: Wagener, Johannes

Regulation of mitochondrial inner membrane fusion: divergent evolution with similar solutions?

• DOI: 10.1007/s00294-015-0542-6
• 发表时间: 2015
• 期刊: Current Genetics
• 影响因子: 2.5
• 作者: J. Wagener