Linked Life Data

20570288

Source:http://linkedlifedata.com/resource/pubmed/id/20570288

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-7-8
pubmed:abstractText
Point mutations in the mitochondrial genome are associated with a variety of metabolic disorders. The myopathy, encephalopathy, lactic acidosis, stroke-like episodes syndrome (MELAS), is most frequently associated with an A to G transition at position 3243 of the mitochondrial tRNA(Leu(UUR)) gene, and is characterized by biochemical and structural alterations of mitochondria. In the present study, we analyzed proteomic changes in an immortalized B-cell line harbouring the MELAS A3243G mutation by two-dimensional difference gel electrophoresis and immunoblot analysis. Although the cell line contained only 10% mutated mitochondrial genomes, we detected significant alterations in numerous proteins associated with the actin cytoskeleton and in nuclear-encoded subunits of mitochondrial respiratory chain complexes. Notably, mitochondrial Lon protease and Hsp60 were deregulated in MELAS cells, indicating an effect on the mitochondrial protein quality control system. By immunofluorescence microscopy, we detected mitochondrial Lon protease accumulation and changes in actin-binding proteins preferentially in MELAS cells containing numerous mitochondria with mutated genomes. Enzymatic assays revealed that Lon protease activity is increased in MELAS cell lysates. Although Lon protease has been shown to degrade misfolded proteins and to stabilize respiratory chain complexes within mitochondria, our MELAS cell line exhibited a higher sensitivity to mitochondrial stress. These findings provide novel insights into the cellular response to dysfunctional mitochondria containing mutated genomes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1878-5883
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
46-52
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Activation of the mitochondrial protein quality control system and actin cytoskeletal alterations in cells harbouring the MELAS mitochondrial DNA mutation.
pubmed:affiliation
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't