Journal
ACS CHEMICAL NEUROSCIENCE
Volume 8, Issue 12, Pages 2759-2765Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.7b00287
Keywords
mitoNEET; mitochondrial dysfunction; aging; drug discovery
Funding
- Richard Nicely and Glenn and Karen Leppo Parkinson's Disease Research Funds
- Stark Community Foundation Canton, Ohio, USA
- Michael J. Fox Foundation
- NIH [U54GM104942, P20GM109098, K01NS081014, R01ES021800]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available