Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators

Julie St-Pierre, Stavit Drori, Marc Uldry, Jessica M. Silvaggi, James Rhee, Sibylle Jäger, Christoph Handschin, Kangni Zheng, Jiandie Lin, Wenli Yang, David K. Simon, Robert Bachoo, Bruce M. Spiegelman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)397-408
Number of pages12
JournalCell
Volume127
Issue number2
DOIs
StatePublished - Oct 20 2006

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Reactive Oxygen Species
Metabolism
Null Lymphocytes
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Peroxisome Proliferator-Activated Receptors
Kainic Acid
Organelle Biogenesis
Substantia Nigra
Enzymes
Electron Transport
RNA Interference
Hippocampus
Respiration
Cell Culture Techniques
Cells
Therapeutics

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., ... Spiegelman, B. M. (2006). Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators. Cell, 127(2), 397-408. https://doi.org/10.1016/j.cell.2006.09.024

Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators. / St-Pierre, Julie; Drori, Stavit; Uldry, Marc; Silvaggi, Jessica M.; Rhee, James; Jäger, Sibylle; Handschin, Christoph; Zheng, Kangni; Lin, Jiandie; Yang, Wenli; Simon, David K.; Bachoo, Robert; Spiegelman, Bruce M.

In: Cell, Vol. 127, No. 2, 20.10.2006, p. 397-408.

Research output: Contribution to journalArticle

St-Pierre, J, Drori, S, Uldry, M, Silvaggi, JM, Rhee, J, Jäger, S, Handschin, C, Zheng, K, Lin, J, Yang, W, Simon, DK, Bachoo, R & Spiegelman, BM 2006, 'Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators', Cell, vol. 127, no. 2, pp. 397-408. https://doi.org/10.1016/j.cell.2006.09.024
St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S et al. Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators. Cell. 2006 Oct 20;127(2):397-408. https://doi.org/10.1016/j.cell.2006.09.024
St-Pierre, Julie ; Drori, Stavit ; Uldry, Marc ; Silvaggi, Jessica M. ; Rhee, James ; Jäger, Sibylle ; Handschin, Christoph ; Zheng, Kangni ; Lin, Jiandie ; Yang, Wenli ; Simon, David K. ; Bachoo, Robert ; Spiegelman, Bruce M. / Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators. In: Cell. 2006 ; Vol. 127, No. 2. pp. 397-408.
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