Linked Life Data

19617636

Source:http://linkedlifedata.com/resource/pubmed/id/19617636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2009-9-23
pubmed:abstractText
Mutations in the parkin gene are the most common cause of recessive familial Parkinson disease (PD). Parkin has been initially characterized as an ubiquitin E3 ligase, but the pathological relevance of this activity remains uncertain. Recently, an impressive amount of evidence has accumulated that parkin is involved in the maintenance of mitochondrial function and biogenesis. We used a human neuroblastoma cell line as a model to study the influence of endogenous parkin on mitochondrial genomic integrity. Using an unbiased chromatin immunoprecipitation approach, we found that parkin is associated physically with mitochondrial DNA (mtDNA) in proliferating as well as in differentiated SH-SY5Y cells. In vivo, the association of parkin with mtDNA could be confirmed in brain tissue of mouse and human origin. Replication and transcription of mtDNA were enhanced in SH-SY5Y cells over-expressing the parkin gene. The ability of parkin to support mtDNA-metabolism was impaired by pathogenic parkin point mutations. Most importantly, we show that parkin protects mtDNA from oxidative damage and stimulates mtDNA repair. Moreover, higher susceptibility of mtDNA to reactive oxygen species and reduced mtDNA repair capacity was observed in parkin-deleted fibroblasts of a PD patient. Our data indicate a novel role for parkin in directly supporting mitochondrial function and protecting mitochondrial genomic integrity from oxidative stress.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3832-50
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair.
pubmed:affiliation
Department for Neurodegenerative Diseases, Center of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't