Mitochondriale Dynamik und Neurotoxizität in Hefe-Zelltodmodellen

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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.