Mitochondriale Dynamik und Neurotoxizität in Hefe-Zelltodmodellen

线粒体是程序性细胞死亡的关键细胞器。它们不断地融合和分裂，并受到降解和生物发生的影响。这些过程影响神经退行性疾病中的神经元功能障碍和细胞死亡。该项目旨在更好地了解这些过程之间调查不足的因果关系。为此，将使用一种易于处理和遗传可处理的酵母细胞系统，其中可以精确分析程序性细胞死亡的分子机制，以及线粒体动力学和周转。我们之前的研究表明，酵母中神经毒性蛋白的表达导致了具有关键线粒体贡献的程序性细胞死亡。在这个项目中，我们将表达与各种神经退行性疾病相关的不同神经毒性蛋白：-我们将描述线粒体损伤和线粒体依赖性细胞死亡途径的诱导。-我们将定义对线粒体形态和动力学的影响，以及它们在执行细胞死亡中的作用。-我们将研究线粒体转换的途径，并剖析其在提供细胞毒性中的作用。我们希望阐明酵母中神经毒性细胞死亡的新细胞机制，从而使这些概念在人类疾病中细胞死亡的其他模型系统中得到有针对性的验证。

Mitochondria are key organelles in programmed cell death. They constantly fuse and divide, and are subject to degradation and biogenesis. These processes influence neuronal dysfunction and cell death in neurodegenerative disorders. This project aims at a better understanding of the poorly investigated causal links between these processes. For this purpose an easy-to-handle and genetically tractable yeast cell system will be used, in which molecular mechanisms of programmed cell death, as well as of mitochondrial dynamics and turnover can be precisely analyzed. Our previous work revealed that expression of neurotoxic proteins in yeast result in programmed cell death with critical mitochondrial contribution. In this project, we will express different neurotoxic proteins associated with various neurodegenerative disorders:- We will describe mitochondrial damage and the induction of mitochondrion-dependent cell death pathways.- We will define the consequences on mitochondrial morphology and dynamics, and their role in executing cell death.- We will investigate pathways of mitochondrial turnover, and dissect their role in providing cytotoxicity.We trust to elucidate novel cellular mechanisms of neurotoxic cell death in yeast, enabling the targeted validation of these concepts in other model systems for cell death in the human disorders.