Document Type
Article
Publication Date
12-20-2017
College/Unit
School of Pharmacy
Department/Program/Center
Pharmaceutical Sciences
Abstract
Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson’s disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron–sulfur containing protein that regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP. Gait analysis revealed a shortened stride length and decreased rotarod performance in knockout mice, consistent with the loss of striatal dopamine. Together, these data suggest that mitoNEET KO mice exhibit many of the characteristics of early neurodegeneration in PD and may provide a novel drug discovery platform to evaluate compounds for enhancing mitochondrial function in neurodegenerative disorders.
Digital Commons Citation
Geldenhuys, Werner J.; Benkovic, Stanley A.; Lin, Li; Yonutas, Heather M.; Crish, Samuel D.; Sullivan, Patrick G.; Darvesh, Altaf S.; Brown, Candice M.; and Richardson, Jason R., "MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype" (2017). Clinical and Translational Science Institute. 862.
https://researchrepository.wvu.edu/ctsi/862
Source Citation
Geldenhuys WJ, Benkovic SA, Lin L, et al. MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson’s Disease Phenotype. ACS Chemical Neuroscience. 2017;8(12):2759-2765. doi:10.1021/acschemneuro.7b00287