Mitochondrial dysfunction and oxidative stress contributes to the death of the brain cells seen in Parkinson’s disease. The mitochondrial protein mitoNEET (encoded by the gene CISD1) has been shown to modulate mitochondrial biology and oxidative capacity. We hypothesize that mitoNEET plays an important role in the oxidative capacity of brain cells and helps maintain normal mitochondrial function. Elimination of mitoNEET from brain cells may show the same mitochondrial dysfunction seen in Parkinson’s disease.
In this project, we will evaluate the effect the loss of mitoNEET has on the mitochondrial function of brain cells. We will evaluate markers of oxidative stress in the brain, as well as the effect the loss of mitoNEET has on the ability of mitochondria to produce ATP (energy). Additionally, we will evaluate the effect oxidative stress might have on the chemical messengers associated with Parkinson’s disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The results from this study will validate the usefulness of mitoNEET as novel drug target in Parkinson’s disease. Novel compounds that can reduce the oxidative stress and mitochondrial dysfunction may be able to slow or stop the progression of Parkinson’s.
We anticipate that the results of this study will show that brain cells where mitoNEET is lacking have similar mitochondrial dysfunction and oxidative stresses that is seen in Parkinson’s patients. These results will form the basis of future studies aimed at understanding the complex signaling pathways in cell survival and cell death associated with brain cell loss.