Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis
Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis
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DOI：
10.1042/cs20160080
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发表时间：
2016-10-01
期刊：
影响因子：
6
通讯作者：
Maria Grau, Josep
中科院分区：
文献类型：
--
作者：
Catalan-Garcia, Marc;Garrabou, Gloria;Maria Grau, Josep
散发包涵体肌炎（sIBM）是老年人最常见的肌病之一。这些患者在组织学水平上存在线粒体异常。我们假设线粒体功能障碍可能在疾病病因学中起作用。我们对30名sIBM患者和38名年龄和性别配对的对照组的肌肉和外周血单个核细胞（PBMCs）进行了以下测量：线粒体DNA （mtDNA）缺失、mtDNA和mtRNA的数量、线粒体蛋白合成、线粒体呼吸链（MRC）复合体I和IV酶活性、线粒体质量、氧化应激和线粒体动力学（丝裂酶2和视神经萎缩1水平）。在sIBM患者的肌肉中存在mtDNA的缺失，pbmc在氧化磷酸化中显示线粒体蛋白的表达失调。MRC复合物IV/柠檬酸合成酶活性显著降低，肌肉线粒体动力学受到影响。mtDNA缺失的患者mtDNA缺失明显更严重，这也表明线粒体融合蛋白的失调。肌肉中线粒体动力学的不平衡与线粒体遗传紊乱（缺失和缺失）的增加有关，表明适当的线粒体更新对于这些患者的线粒体平衡和肌肉功能至关重要。
Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age-and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients.