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GSE5332
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
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.
Publication Title
mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Analysis of brown adipose tissue from Yin Yang 1 (YY1) brown fat specific knockout mice fed a high fat diet for 3 months. YY1 deficiency in brown adipose tissue leads to strong thermogenic deficiency. The goal was to identify the genes controlled by YY1 responsible of brown fat defective function.
Publication Title
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Analysis of visceral white adipose tissue (EWAT) from Yin Yang 1 adipose-specific knockout mice exposed to cold (4C) for 4 days.
Publication Title
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Analysis of subcutaneous adipose tissue (IWAT) from Yin Yang 1 brown fat specific knockout mice fed a high fat diet for 2 weeks. The goal was to identify a gene signature of IWAT browning in YY1 mutant mice.
Publication Title
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus, Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies, having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation.
Publication Title
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies, having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation.
Publication Title
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
PGC1a is a transcriptional coactivator that regulates energy metabolism. PGC1a is highly expressed in a subset of melanoma tumors and cell lines. We generated gene-expression profile of control and PGC1alpha depleted A375P melanoma cells, a melanoma cell line that expresses very high levels of PGC1a to investigate the role of this gene in melanoma.
Publication Title
PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 9 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Expression of the yeast Cth2 protein stimulates degradation of mRNAs encoding proteins with Fe-dependent functions in metabolism, in iron storage and in other cellular processes. We demonstrate that in response to Fe deprivation, the Cth2-homologue, Cth1, stimulates specific degradation of mRNAs involved in mitochondrially localized activities that include respiration and amino acid biosynthesis. Furthermore, yeast cells grown under Fe deprivation accumulate mRNAs encoding proteins that function in glucose metabolism. These studies demonstrate a reprogramming of cellular metabolism during Fe-starvation dependent on the coordinated activities of two mRNA binding proteins.
Publication Title
Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency.
Sample Metadata Fields
No sample metadata fields
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