Mutation in dystrophin-encoding gene affects energy metabolism in mouse myoblasts
Mutation in dystrophin-encoding gene affects energy metabolism in mouse myoblasts
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DOI：
10.1016/j.bbrc.2009.06.053
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发表时间：
2009-08-28
影响因子：
3.1
通讯作者：
Zablocki, Krzysztof
中科院分区：
文献类型：
--
作者：
Onopiuk, Marta;Brutkowski, Wojciech;Zablocki, Krzysztof
杜氏肌营养不良症以分化肌纤维严重缺陷为特征，包括钙稳态异常和细胞能量代谢受损。在这里，我们证明来自营养不良（mdx）小鼠的成肌细胞表现出氧气消耗减少，线粒体膜电位增加，活性氧形成增强，糖酵解受到刺激，但不影响细胞总ATP含量。此外，观察到线粒体呼吸复合物和atp合成酶的特异性亚基数量减少以及线粒体网络紊乱。所使用的营养不良和对照肌母细胞都来自一个共同的近亲繁殖的小鼠品系，它们之间唯一的区别是在营养不良蛋白编码基因上的点突变，因此这些数据表明这种突变导致了多种表型改变，早在未分化的成肌细胞中就表现出来。这一发现揭示了杜氏肌营养不良发病的分子机制。(C) 2009爱思唯尔公司版权所有。
Duchenne Muscular Dystrophy is characterized by severe defects in differentiated Muscle fibers, including abnormal Calcium homeostasis and impaired cellular energy metabolism. Here we demonstrate that myoblasts derived from dystrophic (mdx) mouse exhibit reduced oxygen consumption, increased mitochondrial membrane potential, enhanced reactive oxygen species formation, stimulated glycolysis but unaffected total cellular ATP content. Moreover, reduced amounts Of Specific Subunits of the mitochondrial respiratory complexes and ATP-synthase as well as disorganized mitochondrial network were observed, Both the dystrophic and control myoblasts used were derived from a common inbred mouse strain and the only difference between them is a point Mutation in the dystrophin-encoding gene, thus these data indicate that this mutation results ill Multiple phenotypic alterations demonstrating as early as in undifferentiated myoblasts. This finding sheds new light on the molecular mechanisms of Duchenne Muscular Dystrophy pathogenesis. (C) 2009 Elsevier Inc. All rights reserved.