Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-16
pubmed:abstractText
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 upregulation 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
449-64
pubmed:meshHeading
pubmed-meshheading:19023330-Animals, pubmed-meshheading:19023330-Antioxidants, pubmed-meshheading:19023330-Brain, pubmed-meshheading:19023330-Cell Respiration, pubmed-meshheading:19023330-Corpus Striatum, pubmed-meshheading:19023330-Humans, pubmed-meshheading:19023330-Mice, pubmed-meshheading:19023330-Mice, Knockout, pubmed-meshheading:19023330-Mitochondria, pubmed-meshheading:19023330-Mitochondrial Proteins, pubmed-meshheading:19023330-Molecular Sequence Data, pubmed-meshheading:19023330-Neurons, pubmed-meshheading:19023330-Oxidative Stress, pubmed-meshheading:19023330-Parkinson Disease, pubmed-meshheading:19023330-Reactive Oxygen Species, pubmed-meshheading:19023330-Serine Endopeptidases, pubmed-meshheading:19023330-Tissue Distribution, pubmed-meshheading:19023330-Transcription, Genetic, pubmed-meshheading:19023330-Transcription Factor CHOP
pubmed:year
2009
pubmed:articleTitle
Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response.
pubmed:affiliation
Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester LE1 9HN, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't