TY - JOUR
T1 - MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype
AU - Geldenhuys, Werner J.
AU - Benkovic, Stanley A.
AU - Lin, Li
AU - Yonutas, Heather M.
AU - Crish, Samuel D.
AU - Sullivan, Patrick G.
AU - Darvesh, Altaf S.
AU - Brown, Candice M.
AU - Richardson, Jason R.
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/20
Y1 - 2017/12/20
N2 - 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.
AB - 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.
KW - aging
KW - drug discovery
KW - mitoNEET
KW - mitochondrial dysfunction
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U2 - 10.1021/acschemneuro.7b00287
DO - 10.1021/acschemneuro.7b00287
M3 - Article
C2 - 28880525
AN - SCOPUS:85038588722
VL - 8
SP - 2759
EP - 2765
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 12
ER -