The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy.

Abstract

Heteroplasmic mitochondrial DNA mutations often cause a skeletal myopathy associated with a mosaic distribution of cytochrome c oxidase-deficient muscle fibres. The function of an individual muscle fibre is dependent upon the metabolic activity throughout its length, but little is known about the length of cytochrome c oxidase-deficient segments in human skeletal muscle in patients with mitochondrial disease. We studied cytochrome c oxidase activity by serial section analysis of quadriceps muscle from two patients. We observed a striking variation in the length of the cytochrome c oxidase-negative segments. The shortest segments were 10 microm long, and the longest segment was the entire length of the larger biopsy (> or =1.2 mm). The lengths of the cytochrome c oxidase-negative segments were generally shorter in the less severely affected biopsy, and we frequently observed non-contiguous segments of cytochrome c oxidase deficiency within the same muscle fibre. The findings have important implications for our understanding of the pathogenesis and progression of mitochondrial DNA myopathy.

• Authors: Joanna L Elson, David C Samuels, Margaret A Johnson, Douglass M Turnbull, Patrick F Chinnery
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 12 Issue 9 Pg. 858-64 (Nov 2002) ISSN: 0960-8966 [Print] England
• PMID: 12398838 (Publication Type: Case Reports, Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Mitochondrial
• Electron Transport Complex IV

Topics

• Adult
• Aged
• Aged, 80 and over
• Biopsy
• Blotting, Southern
• Cytochrome-c Oxidase Deficiency
• DNA, Mitochondrial (genetics)
• Electron Transport Complex IV (metabolism)
• Humans
• Immunohistochemistry
• Male
• Mitochondrial Diseases (enzymology, genetics, pathology)
• Mitochondrial Myopathies (enzymology, genetics)
• Muscle Fibers, Skeletal (enzymology, metabolism, pathology)
• Muscle, Skeletal (enzymology, metabolism, pathology)