Cytochrome c oxidase-intermediate fibres: importance in understanding the pathogenesis and treatment of mitochondrial myopathy.
Cytochrome c oxidase-intermediate fibres: importance in understanding the pathogenesis and treatment of mitochondrial myopathy.
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DOI：
10.1016/j.nmd.2012.04.003
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发表时间：
2012-08
影响因子：
2.8
通讯作者：
Turnbull, Doug M.
中科院分区：
文献类型：
--
作者：
Murphy, Julie L.;Ratnaike, Thiloka E.;Shang, Ersong;Falkous, Gavin;Blakely, Emma L.;Alston, Charlotte L.;Taivassalo, Tanja;Haller, Ronald G.;Taylor, Robert W.;Turnbull, Doug M.
线粒体DNA病患者的一个重要诊断肌肉活检发现是呼吸链缺陷纤维的存在。这些纤维在一系列细胞色素c氧化酶-琥珀酸脱氢酶反应后被检测为细胞色素c氧化酶缺乏，通常在细胞色素c氧化酶正常纤维群体中呈马赛克图案。对患有各种线粒体DNA缺陷的患者的肌肉活检的详细分析表明，存在一系列缺陷，因为有大量的纤维既不对应于细胞色素c氧化酶完全正常(棕色染色)，也不对应于细胞色素c氧化酶缺陷(蓝色染色)。我们使用组织化学和免疫细胞化学技术相结合的方法，证明了细胞色素c氧化酶中间反应纤维的数量介于正常纤维和缺陷纤维之间。我们发现，细胞色素c氧化酶中间纤维在突变和野生型线粒体DNA的数量方面也具有不同的遗传特征，因此，可能代表了呼吸正常纤维和呼吸缺陷纤维之间的重要转变。评估中间纤维的变化对于评估对治疗的反应，特别是对线粒体DNA疾病患者的运动训练方案至关重要。
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.
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DOI：
10.1038/nrg1606
发表时间：
2005-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Capaldi, RA;Murray, J;Marusich, MF
通讯作者：
Marusich, MF
影响因子：
9.8
作者：
Durham, Steve E.;Samuels, David C.;Chinnery, Patrick F.
通讯作者：
Chinnery, Patrick F.
影响因子：
14.5
作者：
Murphy, Julie L.;Blakely, Emma L.;Taivassalo, Tanja
通讯作者：
Taivassalo, Tanja
影响因子：
15.9
作者：
Taylor, RW;Barron, MJ;Turnbull, DM
通讯作者：
Turnbull, DM