Mitochondrial genome distribution in histochemically cytochrome c oxidase-negative muscle fibres in patients with a mixture of deleted and wild type mitochondrial DNA.
In situ hybridization studies were performed on a series of chronic progressive external ophthalmoplegia patients harbouring large mitochondrial DNA deletions, using intra- and extra-deletional probes. Clear differences in the distribution of wild type and deleted mitochondrial genomes were seen in both ragged-red and non-ragged red, cytochrome c oxidase-negative fibres, with an accumulation of deleted genomes in the subsarcolemmal zone. Wild type genome content was normal or decreased in the cytochrome c oxidase-negative regions of one case, but in two patients, wild type mtDNA content in cytochrome c oxidase-negative regions was either normal (most fibres) or increased (occasional fibres). The latter observation suggests there may be a stage in the natural history of ragged-red fibre evolution where wild type genomes are transiently increased. The significance of this finding is discussed.
Collins
S
S
Department of Neurology, St. Vincent's Hospital, Melbourne, Australia.
Rudduck
C
C
Marzuki
S
S
Dennett
X
X
Byrne
E
E
D001483:Base Sequence; D001706:Biopsy; D002874:Chromosome Mapping; D015342:DNA Probes; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000302:isolation & purification; D004277:DNA, Single-Stranded; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000302:isolation & purification; D006651:Histocytochemistry; D006801:Humans; D008867:Microtomy; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009886:Ophthalmoplegia / Q000235:genetics*
D015342:DNA Probes; D004272:DNA, Mitochondrial; D004277:DNA, Single-Stranded; D003576:Electron Transport Complex IV