Effects of mitochondrial dynamics genes, fzo-1 and drp-1, on dopaminergic neurodegeneration induced by environmental exposure in Caenorhabditis elegans, as a model of Parkinson’s disease
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Parkinson’s disease (PD) is caused by degeneration of the dopaminergic neurons; environmental toxicants are hypothesized to play a role in PD etiology. Environmental toxicants can cause mitochondrial dysfunction through mitochondrial DNA (mtDNA) damage and production of reactive oxygen species. Serial ultraviolet C (UVC) radiation causes an accumulation of mtDNA damage and 6-hydroxydopamine (6-OHDA) causes loss of dopaminergic neurons. Mitochondrial dynamics, or fusion and fission of the mitochondria, are important processes in mitigating mitochondrial dysfunction. The fzo-1 and drp-1 genes in Caenorhabditis elegans are orthologs for human Mfn1/2 and Drp1 and are involved in mitochondrial fusion and fission, respectively. I tested the hypothesis that deletion mutant strains for these two genes would show increased neurodegeneration after environmental damage, relative to the wild-type control strain, due to the lack of normal mitochondrial dynamics. Unexpectedly, both the fzo-1 and drp-1 were protected against 6-OHDA-induced neurodegeneration relative to wild-type. The fzo-1 knockout underwent complete larval arrest after UVC exposure, suggesting that mitochondrial fusion is necessary for recovery after mtDNA damage. The drp-1 mutant showed slightly more neurodegeneration than wild-type after UVC exposure at the 10 J/m2 dose, but not the 7.5 J/m2 dose. These results highlight the significance of mitochondrial dynamics and gene-environment interactions in dopaminergic neurodegeneration and PD etiology.
DescriptionHonors Thesis submitted for graduation with Distinction in Biology and Environmental Sciences in Trinity College of Duke University
CitationHall, Samantha (2015). Effects of mitochondrial dynamics genes, fzo-1 and drp-1, on dopaminergic neurodegeneration induced by environmental exposure in Caenorhabditis elegans, as a model of Parkinson’s disease. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/10199.
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Rights for Collection: Undergraduate Honors Theses and Student papers