"Alpha-Synuclein Toxicity is Caused by Mitochondrial Dysfunction" by Michael G. Tauro
Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Duennwald, Martin L.

Abstract

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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