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Cytochrome c oxidase-intermediate fibres: Importance in understanding the pathogenesis and treatment of mitochondrial myopathy

Lookup NU author(s): Dr Julie Murphy, Gavin Falkous, Dr Charlotte Alston, Professor Robert Taylor, Emeritus Professor Doug Turnbull



An important diagnostic muscle biopsy finding in patients with mitochondrial DNA disease is the presence of respiratory-chain deficient fibres. These fibres are detected as cytochrome c oxidase-deficient following a sequential cytochrome c oxidase-succinate dehydrogenase reaction, often in a mosaic pattern within a population of cytochrome c oxidase-normal fibres. Detailed analysis of muscle biopsies from patients with various mitochondrial DNA defects shows that a spectrum of deficiency exists, as there are a large number of fibres which do not correspond to being either completely cytochrome c oxidase-normal (brown staining) or cytochrome c oxidase-deficient (blue staining). We have used a combination of histochemical and immunocytochemical techniques to show that a population of cytochrome c oxidase-intermediate reacting fibres are a gradation between normal and deficient fibres. We show that cytochrome c oxidase-intermediate fibres also have different genetic characteristics in terms of amount of mutated and wild-type mtDNA, and as such, may represent an important transition between respiratory normal and deficient fibres. Assessing changes in intermediate fibres will be crucial to evaluating the responses to treatment and in particular to exercise training regimes in patients with mitochondrial DNA disease. (C) 2012 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Murphy JL, Ratnaike TE, Shang ES, Falkous G, Blakely EL, Alston CL, Taivassalo T, Haller RG, Taylor RW, Turnbull DM

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2012

Volume: 22

Issue: 8

Pages: 690-698

Print publication date: 01/08/2012

Date deposited: 31/10/2012

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier Ltd


DOI: 10.1016/j.nmd.2012.04.003


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Funder referenceFunder name
MRC Mitochondrial Disease Cohort Study
UK NHS Highly Specialised Services Commissioners
MRC as part of cross-council Lifelong Health
Muscular Dystrophy Campaign, Newcastle University Centre for Brain Ageing and Vitality
UK NIHR Biomedical Research Centre for Ageing and Age-related disease
906919Wellcome Trust Centre for Mitochondrial Research
G0700718Wellbeing Initiative
RO1-AR050597National Institutes of Health (National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIAMS), USA