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Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions

Nature Genetics volume 1, pages 359–367 (1992)Cite this article

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.

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Author notes

  1. Enzo Ricci

    Present address: Department of Neurology, Universita Cattolica del Sacro Cuore, Rome, Italy

Authors and Affiliations

  1. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, and Department of Genetics and Development, College of Physicians & Surgeons, Columbia University, New York, New York, 10032, USA

    Carlos T. Moraes & Eric A. Schon

  2. H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, Department of Neurology, College of Physicians & Surgeons, Columbia University, New York, New York, 10032, USA

    Enzo Ricci, Vittoria Petruzzella, Sara Shanske, Salvatore DiMauro, Eric A. Schon & Eduardo Bonilla

Authors
  1. Carlos T. Moraes
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  2. Enzo Ricci
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  4. Sara Shanske
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  5. Salvatore DiMauro
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  6. Eric A. Schon
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Moraes, C., Ricci, E., Petruzzella, V. et al. Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. Nat Genet 1, 359–367 (1992). https://doi.org/10.1038/ng0892-359

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