Parkinson's disease (PD) is the second most common neurodegenerative disease affecting approximately 10 million people worldwide. While the pathogenesis of PD is incompletely understood a crucial role for the mitochondria is suggested by the fact that PD patients exhibit deficits in the mitochondrial electron transport chain, that mitochondrial toxins have been used as a model of the disease, and that genes involved in mitochondrial function have been shown to cause monogenic forms of PD. In this work, we use C. elegans to study the effect of three mitochondria-related genes, which have been implicated in PD (
pdr-1,
pink-1 and
djr-1.1.), on mitochondrial morphology, mitochondrial function, dopamine neuron survival, and dopamine neuronal function. We found
pdr-1 mutants exhibit deficits in dopamine-dependent behaviors, including basal slowing and ethanol avoidance, but no loss of dopamine neurons. In contrast, we did not observe any significant differences in
pink-1 mutants, while
djr-1.1 mutants only showed an increased sensitivity to oxidative stress. In examining mitochondrial morphology and function, we found that
djr-1.1 mutants exhibit increased mitochondrial fragmentation leading to decreased rate of oxidative phosphorylation and decreased ATP levels.
pdr-1 and
pink-1 mutants show an accumulation of mitochondria with age. In
pdr-1 mutants this leads to an increase in oxidative phosphorylation but decreased levels of ATP, suggesting an increase in damaged mitochondria. Consistent with this conclusion, we observed a marked activation of the mitochondrial unfolded protein response (mitoUPR) in both
pdr-1 and
pink-1 mutants. To determine if the activation of mitoUPR is acting to protect the dopamine neurons from dysfunction and death, we crossed
pdr-1 and
pink-1 mutants to an
atfs-1 deletion mutant, which is unable to activate the mitoUPR. Our preliminary results show a trend towards increased neuronal loss in the
pdr-1 and
pink-1 mutants when the mitoUPR is blocked, suggesting that the upregulation of the mitoUPR acts to protect the dopamine neurons from degeneration and death. Overall, our results suggest that mutations in
pdr-1 and
pink-1 cause the accumulation of damaged mitochondria, which activates the mitoUPR to mitigate the detrimental effect of these mutations on the dopamine neurons thereby resulting in only mild PD-like deficits in these mutants.