Mitochondrial myopathy: correlation between oxidative defect and mitochondrial DNA deletions at single fiber level
| Autor: | Nicoletta Checcarelli, Massimo Zeviani, Guglielmo Scarlato, Alessandro Battistel, Giacomo P. Comi, Maurizio Moggio, Andreina Bordoni, P. Bazzi, Alessandro Prelle, Gigliola Fagiolari |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male Mitochondrial DNA Adolescent Cytochrome-c Oxidase Deficiency In situ hybridization Mitochondrion DNA Mitochondrial Pathology and Forensic Medicine law.invention Cellular and Molecular Neuroscience chemistry.chemical_compound Nerve Fibers Mitochondrial myopathy law medicine Cytochrome c oxidase Humans Ragged red fibers Polymerase chain reaction In Situ Hybridization Aged Immunohistochemistry Female Middle Aged Mitochondrial Myopathies Muscles Gene Deletion biology DNA medicine.disease Molecular biology eye diseases Mitochondrial Nuclear DNA chemistry biology.protein Neurology (clinical) |
| Zdroj: | Acta neuropathologica. 87(4) |
| ISSN: | 0001-6322 |
| Popis: | In situ hybridization combined with immunohistochemical techniques has been applied to study patients affected by mitochondrial myopathies with large mitochondrial (mt)DNA deletions. All patients' muscle biopsies showed ragged red fibers (RRFs) and cytochrome oxidase (COX) deficiency. Two digoxigenin-labeled, polymerase chain reaction (PCR)-amplified DNAs were used as probes. One probe was designed to hybridize only with wild-type mtDNAs, while the other recognized both wild-type and deleted mtDNAs. Concomitant immunocytochemical analysis using antibodies against subunits II, III, (encoded by mtDNA) and IV (encoded by nuclear DNA) of COX was carried out. In our patients deleted mtDNAs are overexpressed in COX-negative RRFs, while wild-type mtDNAs are decreased in the same fibers. Immunohistochemistry studies show that COX IV is overexpressed in RRFs and that COX II and COX III subunits are still present. Deleted mtDNAs are spatially segregated in muscle fibers, where they interfere with the local population of normal mitochondrial genomes, causing a regional deficiency of the mitochondrial respiratory activity. |
| Databáze: | OpenAIRE |
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