TY - JOUR
T1 - Cytochrome c oxidase-intermediate fibres
T2 - Importance in understanding the pathogenesis and treatment of mitochondrial myopathy
AU - Murphy, Julie L.
AU - Ratnaike, Thiloka E.
AU - Shang, Ersong
AU - Falkous, Gavin
AU - Blakely, Emma L.
AU - Alston, Charlotte L.
AU - Taivassalo, Tanja
AU - Haller, Ronald G.
AU - Taylor, Robert W.
AU - Turnbull, Doug M.
N1 - Funding Information:
This work was supported by the The Muscular Dystrophy Campaign, Newcastle University Centre for Brain Ageing and Vitality supported by BBSRC, EPSRC, ESRC and MRC as part of the cross-council Lifelong Health and Wellbeing Initiative ( G0700718 ), MRC Mitochondrial Disease Cohort Study, The Wellcome Trust Centre for Mitochondrial Research ( 906919 ), UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, the UK NHS Highly Specialised Services Commissioners which funds the “Rare Mitochondrial Disorders of Adults and Children” Diagnostic Service in Newcastle upon Tyne ( http://www.mitochondrialncg.nhs.uk ) and by the National Institutes of Health (National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIAMS, RO1-AR050597), USA.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Cytochrome c oxidase
KW - Enzyme histochemistry
KW - Mitochondrial myopathy
KW - MtDNA
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U2 - 10.1016/j.nmd.2012.04.003
DO - 10.1016/j.nmd.2012.04.003
M3 - Article
C2 - 22647770
AN - SCOPUS:84863874248
SN - 0960-8966
VL - 22
SP - 690
EP - 698
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 8
ER -