TY - JOUR
T1 - Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators
AU - St-Pierre, Julie
AU - Drori, Stavit
AU - Uldry, Marc
AU - Silvaggi, Jessica M.
AU - Rhee, James
AU - Jäger, Sibylle
AU - Handschin, Christoph
AU - Zheng, Kangni
AU - Lin, Jiandie
AU - Yang, Wenli
AU - Simon, David K.
AU - Bachoo, Robert
AU - Spiegelman, Bruce M.
N1 - Funding Information:
J.S. was a recipient of a Jane Coffin Childs Fellowship and a Canadian Institutes of Health Research Fellowship. D.K.S. and K.Z. are supported in part by NINDS grant K02 NS4311. This research was supported by NIH grant DK54477 to B.M.S.
PY - 2006/10/20
Y1 - 2006/10/20
N2 - PPARγ coactivator 1α (PGC-1α) is a potent stimulator of mitochondrial biogenesis and respiration. Since the mitochondrial electron transport chain is the main producer of reactive oxygen species (ROS) in most cells, we examined the effect of PGC-1α on the metabolism of ROS. PGC-1α is coinduced with several key ROS-detoxifying enzymes upon treatment of cells with an oxidative stressor; studies with RNAi or null cells indicate that PGC-1α is required for the induction of many ROS-detoxifying enzymes, including GPx1 and SOD2. PGC-1α null mice are much more sensitive to the neurodegenerative effects of MPTP and kainic acid, oxidative stressors affecting the substantia nigra and hippocampus, respectively. Increasing PGC-1α levels dramatically protects neural cells in culture from oxidative-stressor-mediated death. These studies reveal that PGC-1α is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins.
AB - PPARγ coactivator 1α (PGC-1α) is a potent stimulator of mitochondrial biogenesis and respiration. Since the mitochondrial electron transport chain is the main producer of reactive oxygen species (ROS) in most cells, we examined the effect of PGC-1α on the metabolism of ROS. PGC-1α is coinduced with several key ROS-detoxifying enzymes upon treatment of cells with an oxidative stressor; studies with RNAi or null cells indicate that PGC-1α is required for the induction of many ROS-detoxifying enzymes, including GPx1 and SOD2. PGC-1α null mice are much more sensitive to the neurodegenerative effects of MPTP and kainic acid, oxidative stressors affecting the substantia nigra and hippocampus, respectively. Increasing PGC-1α levels dramatically protects neural cells in culture from oxidative-stressor-mediated death. These studies reveal that PGC-1α is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins.
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U2 - 10.1016/j.cell.2006.09.024
DO - 10.1016/j.cell.2006.09.024
M3 - Article
C2 - 17055439
AN - SCOPUS:33749999530
SN - 0092-8674
VL - 127
SP - 397
EP - 408
JO - Cell
JF - Cell
IS - 2
ER -