|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
Pt 3
|
|
pubmed:dateCreated |
2005-4-22
|
|
pubmed:abstractText |
Two mutations (G8363A and A8296G) in the mtDNA (mitochondrial DNA) tRNA(Lys) gene have been associated with severe mitochondrial diseases in a number of reports. Their functional significance, however, remains unknown. We have already shown that homoplasmic cybrids harbouring the A8296G mutation display normal oxidative phosphorylation, although the possibility of a subtle change in mitochondrial respiratory capacity remains an open issue. We have now investigated the pathogenic mechanism of another mutation in the tRNA(Lys) gene (G8363A) by repopulating an mtDNA-less human osteosarcoma cell line with mitochondria harbouring either this genetic variant alone or an unusual combination of the two mutations (A8296G+G8363A). Cybrids homoplasmic for the single G8363A or the A8296G+G8363A mutations have defective respiratory-chain enzyme activities and low oxygen consumption, indicating a severe impairment of the oxidative phosphorylation system. Generation of G8363A cybrids within a wild-type or the A8296G mtDNA genetic backgrounds resulted in an important alteration in the conformation of the tRNA(Lys), not affecting tRNA steady-state levels. Moreover, mutant cybrids have an important decrease in the proportion of amino-acylated tRNA(Lys) and, consequently, mitochondrial protein synthesis is greatly decreased. Our results demonstrate that the pathogenicity of the G8363A mutation is due to a change in the conformation of the tRNA that severely impairs aminoacylation in the absence of changes in tRNA stability. The only effect detected in the A8296G mutation is a moderate decrease in the aminoacylation capacity, which does not affect mitochondrial protein biosynthesis.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10102446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10514449,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10660592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10675086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10699169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10699170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10737988,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10858457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-10924280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-11223238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-11857739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-12504210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-12737626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-12826641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-12889661,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-12914686,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-1378759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-14719536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-2461720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-2814477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-7647790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-8651277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-8773598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-8965692,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-8965693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-9052804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-9372914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-9571188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-9802769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-9817933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-9889270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15554876-9932960
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1470-8728
|
|
pubmed:author |
pubmed-author:ArenasJoaquínJ,
pubmed-author:BornsteinBelénB,
pubmed-author:CamposYolandaY,
pubmed-author:CarrozzoRosalbaR,
pubmed-author:Fernández-MorenoMiguel AngelMA,
pubmed-author:GaresseRafaelR,
pubmed-author:González-VioqueEmilianoE,
pubmed-author:MartínMiguel AngelMA,
pubmed-author:MasJosé AntonioJA,
pubmed-author:PatronoClariceC,
pubmed-author:SantorelliFilippo MFM,
pubmed-author:del HoyoPilarP
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
|
pubmed:volume |
387
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
773-8
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:15554876-Aminoacylation,
pubmed-meshheading:15554876-Cell Line, Tumor,
pubmed-meshheading:15554876-DNA, Mitochondrial,
pubmed-meshheading:15554876-Gene Expression Regulation,
pubmed-meshheading:15554876-Humans,
pubmed-meshheading:15554876-MERRF Syndrome,
pubmed-meshheading:15554876-Mitochondria,
pubmed-meshheading:15554876-Mutation,
pubmed-meshheading:15554876-Phenotype,
pubmed-meshheading:15554876-Protein Conformation,
pubmed-meshheading:15554876-RNA, Transfer, Lys
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Comparative analysis of the pathogenic mechanisms associated with the G8363A and A8296G mutations in the mitochondrial tRNA(Lys) gene.
|
|
pubmed:affiliation |
Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|
