Developmental and Pathological Changes in the Human Cardiac Muscle Mitochondrial DNA Organization, Replication and Copy Number
| Autor: | Pekka J. Karhunen, Howard T. Jacobs, Jaakko L. O. Pohjoismäki, Steffi Goffart, Douglas M. Turnbull, Anu Suomalainen, Robert W. Taylor |
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| Přispěvatelé: | University of Tampere, Research Programs Unit, Research Programme for Molecular Neurology, Department of Neurosciences |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
ALPERS-SYNDROME
Male Mitochondrial Diseases lcsh:Medicine Mitochondrion medicine.disease_cause Mice 0302 clinical medicine Lääketieteen bioteknologia - Medical biotechnology FAILURE lcsh:Science Child Genetics Aged 80 and over Recombination Genetic 0303 health sciences Mutation Multidisciplinary Cardiac muscle Middle Aged Phenotype 3. Good health medicine.anatomical_structure MULTIPLE MTDNA DELETIONS Child Preschool Cardiovascular Disorders/Myopathies Female Cardiovascular Disorders/Myocardial Infarction PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA Research Article Adult DNA Replication Mitochondrial DNA Adolescent DNA Copy Number Variations Heart Diseases Mitochondrial disease Heart Ventricles education Biology DNA Mitochondrial Mitochondrial Proteins 03 medical and health sciences medicine Animals Humans 030304 developmental biology Molecular Biology/DNA Replication Aged TRANSCRIPTION FACTOR-A Molecular Biology/Recombination Molecular Biology/DNA Repair MUTATIONS HUMAN-CELLS Point mutation Myocardium lcsh:R DNA replication DNA Helicases Infant Newborn Infant Developmental Biology/Aging medicine.disease DNA Polymerase I HUMAN HEART Case-Control Studies HELICASE TWINKLE lcsh:Q AUTOSOMAL-DOMINANT 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 5, p e10426 (2010) |
| Popis: | Adult human heart mitochondrial DNA (mtDNA) has recently been shown to have a complex organization with abundant dimeric molecules, branched structures and four-way junctions. In order to understand the physiological significance of the heart-specific mtDNA maintenance mode and to find conditions that modify human heart mtDNA structure and replication, we analyzed healthy human heart of various ages as well as several different heart diseases, including ischemic heart disease, dilated as well as hypertrophic cardiomyopathies, and several mitochondrial disorders. By using one- and two-dimensional agarose gel electrophoresis, various enzymatic treatments and quantitative PCR we found that in human newborns heart mtDNA has a simple organization, lacking junctional forms and dimers. The adult-type branched forms are acquired in the early childhood, correlating with an increase in mtDNA copy number. Mitochondrial disorders involving either mutations in the mtDNA polymerase γ (PolGα) or mtDNA helicase Twinkle, while having no obvious cardiac manifestation, show distinct mtDNA maintenance phenotypes, which are not seen in various types of diseased heart or in mitochondrial disorders caused by point mutations or large-scale deletions of mtDNA. The findings suggest a link between cardiac muscle development, mtDNA copy number, replication mode and topological organization. Additionally, we show that Twinkle might have a direct role in the maintenance of four-way junctions in human heart mtDNA. Public Library of Science |
| Databáze: | OpenAIRE |
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