title: Distribution of wild-type and common deletion forms of mtDNA in normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy.
abstract: We studied the cellular distribution of both deleted (delta) and wild-type (wt) mitochondrial DNAs (mtDNAs) in 'normal' and respiration-deficient muscle fibers from four patients with mitochondrial myopathy. PCR-based methods were used to quantitate both relative and absolute amounts of delta- and wt-mtDNAs in microdissected fiber segments. Although delta-mtDNAs were present in normal fibers (31% +/- 26), their percentages were much higher in affected fibers (95% +/- 2). Absolute levels of delta-mtDNA were also increased in affected fibers, whereas levels of wt-mtDNA were significantly reduced in these fibers. These results indicate that a threshold ratio of delta-/wt-mtDNA must be achieved before an impairment of respiration is observed in muscle. Moreover, the marked reduction in wt-mtDNA observed in affected fibers suggests that absolute amounts of mtDNA may play a role in the pathogenesis of mitochondrial myopathies.
authors.affiliation: H. Houston Merritt Clinical Research Center for Muscular Dystrophy, Columbia University, New York, NY 10032.
authors.forename: M
authors.initials: M
authors.lastname: Sciacco
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
authors.forename: C T
authors.initials: CT
authors.lastname: Moraes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D030401:Cytochrome-c Oxidase Deficiency; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics; D017241:MELAS Syndrome / Q000235:genetics; D017243:MERRF Syndrome / Q000235:genetics; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000201:enzymology / Q000235:genetics*; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption; D016133:Polymerase Chain Reaction / Q000379:methods; D015183:Restriction Mapping; D017384:Sequence Deletion; D013385:Succinate Dehydrogenase / Q000032:analysis
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV