Linked Life Data

12351217

Source:http://linkedlifedata.com/resource/pubmed/id/12351217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-9-27
pubmed:abstractText
To clarify the importance of deleted protein and tRNA genes on the impairment of mitochondrial function, we performed a quantitative analysis of biochemical, genetic and morphological findings in skeletal muscles of 16 patients with single deletions and 5 patients with multiple deletions of mtDNA. Clinically, all patients showed chronic progressive external ophthalmoplegia (CPEO). The size of deletions varied between 2.5 and 9 kb, and heteroplasmy between 31% and 94%. In patients with single deletions, the citrate synthase (CS) activity was nearly doubled. Decreased ratios of pyruvate- and succinate-dependent respiration were detected in fibers of all patients in comparison to controls. Inverse and linear correlations without thresholds were established between heteroplasmy and (i) CS referenced activities of the complexes of respiratory chain, (ii) CS referenced maximal respiratory rates, (iii) and cytochrome-c-oxidase (COX) negative fibers. In patients with single and multiple deletions, all respiratory chain complexes as well as the respiratory rates were decreased to a similar extent. All changes detected in patients with single deletions were independent of deletion size. In one patient, only genes of ND5, ND4L as well as tRNA(Leu(CUN)), tRNA(Ser(AGY)), and tRNA(His) were deleted. The pronounced decrease in COX activity in this patient points to the high pathological impact of these missing tRNA genes. The activity of nuclear encoded SDH was also significantly decreased in patients, but to a lesser extent. This is an indication of secondary disturbances of mitochondria at CPEO. In conclusion, we have shown that different deletions cause mitochondrial impairments of the same phenotype correlating with heteroplasmy. The missing threshold at the level of mitochondrial function seems to be characteristic for large-scale deletions were tRNA and protein genes are deleted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
1556
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-52
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed-meshheading:12351217-Citrate (si)-Synthase, pubmed-meshheading:12351217-DNA, Mitochondrial, pubmed-meshheading:12351217-Electron Transport, pubmed-meshheading:12351217-Electron Transport Complex I, pubmed-meshheading:12351217-Electron Transport Complex III, pubmed-meshheading:12351217-Female, pubmed-meshheading:12351217-Gene Deletion, pubmed-meshheading:12351217-Humans, pubmed-meshheading:12351217-Male, pubmed-meshheading:12351217-Middle Aged, pubmed-meshheading:12351217-Mitochondria, Muscle, pubmed-meshheading:12351217-Mitochondrial Proteins, pubmed-meshheading:12351217-Muscle, Skeletal, pubmed-meshheading:12351217-NADH, NADPH Oxidoreductases, pubmed-meshheading:12351217-Ophthalmoplegia, Chronic Progressive External, pubmed-meshheading:12351217-Oxygen Consumption, pubmed-meshheading:12351217-Regression Analysis, pubmed-meshheading:12351217-Succinate Dehydrogenase
pubmed:year
2002
pubmed:articleTitle
Mitochondrial respiratory rates and activities of respiratory chain complexes correlate linearly with heteroplasmy of deleted mtDNA without threshold and independently of deletion size.
pubmed:affiliation
Muskellabor der Neurologischen Klinik der Martin-Luther-Universität Halle-Wittenb., Julius-Kühn-Strasse 7, D-06079, Halle an der Saale, Germany. frank.gellerich@medizin.uni-halle.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't