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| Status |
Public on Dec 01, 2008 |
| Title |
Mitochondrial dysfunction by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Cellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinson’s disease patients’ brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.
This SuperSeries is composed of the SubSeries listed below.
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| Overall design |
Refer to individual Series
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| |
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| Citation(s) |
19023330 |
| |
| Submission date |
Oct 03, 2008 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Kristina Klupsch |
| Organization name |
Cancer Research UK
|
| Department |
London Research Institute
|
| Lab |
Signal Transduction Laboratory
|
| Street address |
44 Lincoln's Inn Fields
|
| City |
London |
| ZIP/Postal code |
WC2A 3PX |
| Country |
United Kingdom |
| |
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| Platforms (2) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (18)
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| This SuperSeries is composed of the following SubSeries: |
| GSE13033 |
Differentially expressed genes in brain tissue from HtrA2 knockout mice |
| GSE13034 |
Differentially regulated genes in HtrA2 knockout MEFs upon rotenone treatment |
|
| Relations |
| BioProject |
PRJNA109707 |
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