Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions

Carlos T. Moraes, Enzo Ricci, Vittoria Petruzzella, Sara Shanske, Salvatore DiMauro, Eric A. Schon, Eduardo Bonilla

Research output: Contribution to journalArticle

140 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)359-367
Number of pages9
JournalNature genetics
Volume1
Issue number5
DOIs
StatePublished - Aug 1992
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Moraes, C. T., Ricci, E., Petruzzella, V., Shanske, S., DiMauro, S., Schon, E. A., & Bonilla, E. (1992). Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. Nature genetics, 1(5), 359-367. https://doi.org/10.1038/ng0892-359