title: Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions.
abstract: Large-scale deletions of mitochondrial DNA (mtDNA) are associated with a subgroup of mitochondrial encephalomyopathies. We studied seven patients with Kearns-Sayre syndrome or isolated ocular myopathy who harboured a sub-population of partially-deleted mitochondrial genomes in skeletal muscle. Variable cytochrome c oxidase (COX) deficiencies and reduction of mitochondrially-encoded polypeptides were found in affected muscle fibres, but while many COX-deficient fibres had increased levels of mutant mtDNA, they almost invariably had reduced levels of normal mtDNA. Our results suggest that a specific ratio between mutant and wild-type mitochondrial genomes is the most important determinant of a focal respiratory chain deficiency, even though absolute copy numbers may vary widely.
authors.affiliation: H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, New York, New York.
authors.forename: C T
authors.initials: CT
authors.lastname: Moraes
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: V
authors.initials: V
authors.lastname: Petruzzella
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
mesh_terms: D015139:Blotting, Southern; D030401:Cytochrome-c Oxidase Deficiency; D015342:DNA Probes; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007625:Kearns-Sayre Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017241:MELAS Syndrome / Q000235:genetics; D017243:MERRF Syndrome / Q000235:genetics; D017240:Mitochondrial Myopathies / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D009801:Oculomotor Muscles / Q000201:enzymology / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000032:analysis / Q000235:genetics; D000077278:RNA, Mitochondrial; D017384:Sequence Deletion; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: D015342:DNA Probes; D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012313:RNA; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV