Linked Life Data

17167074

Source:http://linkedlifedata.com/resource/pubmed/id/17167074

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-2-1
pubmed:abstractText
Friedreich ataxia (FA), the most common form of hereditary ataxia, is caused by a deficit in the mitochondrial protein frataxin. While several hypotheses have been suggested, frataxin function is not well understood. Oxidative stress has been suggested to play a role in the pathophysiology of FA, but this view has been recently questioned, and its link to frataxin is unclear. Here, we report the use of RNA interference (RNAi) to suppress the Drosophila frataxin gene (fh) expression. This model system parallels the situation in FA patients, namely a moderate systemic reduction of frataxin levels compatible with normal embryonic development. Under these conditions, fh-RNAi flies showed a shortened life span, reduced climbing abilities, and enhanced sensitivity to oxidative stress. Under hyperoxia, fh-RNAi flies also showed a dramatic reduction of aconitase activity that seriously impairs the mitochondrial respiration while the activities of succinate dehydrogenase, respiratory complex I and II, and indirectly complex III and IV are normal. Remarkably, frataxin overexpression also induced the oxidative-mediated inactivation of mitochondrial aconitase. This work demonstrates, for the first time, the essential function of frataxin in protecting aconitase from oxidative stress-dependent inactivation in a multicellular organism. Moreover our data support an important role of oxidative stress in the progression of FA and suggest a tissue-dependent sensitivity to frataxin imbalance. We propose that in FA, the oxidative mediated inactivation of aconitase, which occurs normally during the aging process, is enhanced due to the lack of frataxin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
333-44
pubmed:meshHeading
pubmed-meshheading:17167074-Aconitate Hydratase, pubmed-meshheading:17167074-Animals, pubmed-meshheading:17167074-Blotting, Western, pubmed-meshheading:17167074-CHO Cells, pubmed-meshheading:17167074-Cricetinae, pubmed-meshheading:17167074-Cricetulus, pubmed-meshheading:17167074-Drosophila Proteins, pubmed-meshheading:17167074-Drosophila melanogaster, pubmed-meshheading:17167074-Electron Transport Complex I, pubmed-meshheading:17167074-Friedreich Ataxia, pubmed-meshheading:17167074-Gene Expression, pubmed-meshheading:17167074-Immunohistochemistry, pubmed-meshheading:17167074-Iron-Binding Proteins, pubmed-meshheading:17167074-Longevity, pubmed-meshheading:17167074-Mitochondrial Proteins, pubmed-meshheading:17167074-Oxidative Stress, pubmed-meshheading:17167074-RNA, Messenger, pubmed-meshheading:17167074-RNA Interference, pubmed-meshheading:17167074-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17167074-Succinate Dehydrogenase
pubmed:year
2007
pubmed:articleTitle
Causative role of oxidative stress in a Drosophila model of Friedreich ataxia.
pubmed:affiliation
Departament de Genètica, Universitat de València, Carrer Doctor Moliner 50, 46100-Burjassot, Valencia, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't