Publication Date

2023

Document Type

Thesis

Committee Members

Quan Zhong, Ph.D. (Advisor); Lynn Hartzler, Ph.D. (Committee Member); Hongmei Ren, Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Although α-synuclein (α-syn) has been linked genetically and pathologically to Parkinson’s disease, the mechanism by which it drives disease pathogenesis is not fully understood. When α-syn is overexpressed in yeast, it forms abnormal cytoplasmic accumulations and leads to cell death, resembling the phenotypes observed in neurons. Such yeast models have been widely used to uncover molecular mechanisms of α-syn toxicity, but the induction of α-syn relies on growing yeast in galactose, a fermentable carbon source. Yeast does not require cellular respiration when grown in galactose, thus limiting the understanding of α-syn toxicity when cellular respiration is essential for neurons. We developed a new model that expresses α-syn under the respiratory condition. We observed striking mitochondrial defects correlated with α-syn accumulation and toxicity. We also identified human and yeast genes that suppress α-syn toxicity and reduce mitochondrial damage. Our data support using a respiratory cell model to study mitochondria-associated α-syn toxicity.

Page Count

98

Department or Program

Department of Biological Sciences

Year Degree Awarded

2023


Included in

Biology Commons

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