| dc.description.abstract |
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.
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