Electronic Thesis and Dissertation Repository


Master of Science




Duennwald, Martin L.


Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting roughly 1% of the population over the age of sixty years. Alpha-synuclein (aSyn) is a protein implicated in both familial and idiopathic forms of PD, yet despite the wealth of data implicating aSyn as a causative agent in PD, the mechanisms underlying its toxicity remain mostly unknown. Mitochondrial dysfunction is a major hallmark of PD, yet there is only limited evidence linking aSyn toxicity to mitochondrial dysfunction. My study establishes a novel aSyn model in respiring yeast cells, which allows me to explore how aSyn affects mitochondrial homeostasis and function. My data shows that mitochondrial fission and fusion, ER-mitochondria communication, and sphingolipid metabolism, interact genetically with aSyn toxicity. My work, therefore, indicates that aSyn impairs mitochondrial homeostasis, which might be a key contributor to neurodegeneration in PD.

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