MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype.

Title

MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype.

Creator

Geldenhuys Werner J; Benkovic Stanley A; Lin Li; Yonutas Heather M; Crish Samuel D; Sullivan Patrick G; Darvesh Altaf S; Brown Candice M; Richardson Jason R

Publisher

ACS chemical neuroscience

Date

2017
2017-12

Description

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.

Subject

*aging; *Disease Models; *drug discovery; *mitochondrial dysfunction; *mitoNEET; Animal; Animals; Corpus Striatum/*metabolism/*pathology; Inbred C57BL; Iron-Binding Proteins/genetics/*metabolism; Knockout; Male; Membrane Proteins/genetics/*metabolism; Mice; Mitochondria/*metabolism/*pathology; Parkinson Disease/*metabolism/pathology

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

2759–2765

Issue

12

Volume

8

Citation

Geldenhuys Werner J; Benkovic Stanley A; Lin Li; Yonutas Heather M; Crish Samuel D; Sullivan Patrick G; Darvesh Altaf S; Brown Candice M; Richardson Jason R, “MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype.,” NEOMED Bibliography Database, accessed January 20, 2021, https://neomed.omeka.net/items/show/3970.

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