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Series GSE5332 Query DataSets for GSE5332
Status Public on Dec 01, 2007
Title mTOR pathway controls mitochondrial gene expression and respiration through the YY1/PGC-1alpha transcriptional complex
Organism Mus musculus
Experiment type Expression profiling by array
Summary Mitochondrial oxidative function is tightly controlled to maintain energy homeostasis in response to nutrient and hormonal signals. An important cellular component in the energy sensing response is the target of rapamycin (TOR) kinase pathway; however whether and how mTOR controls mitochondrial oxidative activity is unknown. Here, we show that mTOR kinase activity stimulates mitochondrial gene expression and oxidative function. In skeletal muscle cells and TSC2-/- MEFs, the mTOR inhibitor rapamycin largely decreased gene expression of mitochondrial transcriptional regulators such as PGC-1alpha and the transcription factors ERRalpha and NRFs. As a consequence, mitochondrial gene expression and oxygen consumption were reduced upon mTOR inhibition. Using computational genomics, we identified the transcription factor YY1 as a common target of mTOR and PGC-1alpha that controls mitochondrial gene expression. Inhibition of mTOR resulted in a failure of YY1 to interact and be coactivated by PGC-1alpha. Notably, knock-down of YY1 in skeletal muscle cells caused a significant decrease in mRNAs of mitochondrial regulators and mitochondrial genes that resulted in a decrease in respiration. Moreover, YY1 was required for rapamycin-dependent repression of mitochondrial genes. Thus, we have identified a novel mechanism in which a nutrient sensor (mTOR) balances energy metabolism via transcriptional control of mitochondrial oxidative function. These results have important implications for our understanding of how these pathways might be altered in metabolic diseases and cancer.
Keywords: comparative genomics, drug treatment response
 
Overall design Using Affymetrix MOE430 v2 gene chips, biological triplicates of each condition were analyzed: vehicle-treated, rapamycin-treated, gfp-infected, and pgc-1alpha-infected resulting in a total of 12 samples.

Data were analyzed by RMA (with default settings) in BioConductor 1.2 -- one batch for the Rapamycin vs. Vehicle, and another batch for the PGC vs GFP.
 
Contributor(s) Cunningham JT, Arlow D, Vazquez F, Mootha VK, Puigserver P
Citation(s) 18046414
Submission date Jul 18, 2006
Last update date Feb 11, 2019
Contact name Pere Puigserver
E-mail(s) Pere_Puigserver@dfci.harvard.edu
Phone 617-582-7977
Organization name Dana-Farber Cancer Institute
Department Cancer Biology
Lab Smith 936
Street address 1 Jimmy Fund Way
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (12)
GSM120798 Control 1
GSM120811 Control 2
GSM120812 Control 3
Relations
BioProject PRJNA96347

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE5332_RAW.tar 74.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file

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