MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson’s Disease Phenotype
| Autor: | Heather M. Yonutas, Samuel D. Crish, Stanley A. Benkovic, Candice M. Brown, Li Lin, Altaf S. Darvesh, Patrick G. Sullivan, Jason R. Richardson, Werner J. Geldenhuys |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Parkinson's disease Bioenergetics Physiology Cognitive Neuroscience Mitochondrion Biology Biochemistry Article 03 medical and health sciences Mice Internal medicine Iron-Binding Proteins medicine Animals chemistry.chemical_classification Mice Knockout Reactive oxygen species Tyrosine hydroxylase Neurodegeneration Membrane Proteins Parkinson Disease Cell Biology General Medicine medicine.disease Phenotype Corpus Striatum Mitochondria Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology chemistry Knockout mouse Neuroscience |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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