Mitochondrial defects in cardiomyopathy and neuromuscular disease
Mitochondrial defects in cardiomyopathy and neuromuscular disease
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DOI：
10.1067/mhj.2000.103934
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发表时间：
2000-02-01
影响因子：
4.8
通讯作者：
Wallace, DC
中科院分区：
文献类型：
--
作者：
Wallace, DC
在过去的11年里，大量的证据表明线粒体能量产生途径的缺陷，氧化磷酸化，与包括肌病和心肌病在内的各种退行性疾病有关。大多数类型的致病线粒体DNA突变会影响心脏，并与她的各种临床表现有关，包括骨骼肌、中枢神经系统(包括眼睛)、内分泌系统和肾脏系统。为了更好地了解线粒体疾病的病理生理学基础及其在肌病和心肌病中的作用，已经制备了几种线粒体疾病的小鼠模型。来自培养细胞的线粒体DNA突变已被引入小鼠；参与线粒体能量产生和活性氧物种解毒的核DNA基因已被基因失活，导致小鼠分别患有肥厚性心肌病和扩张型心肌病。这些小鼠的生理特征已经证实了线粒体能量产生减少，线粒体活性氧产生增加，以及线粒体启动细胞凋亡在线粒体疾病中的重要性。根据这些见解，已经提出了治疗神经肌肉和心脏疾病的新方法。
Over the past 11 years, a considerable body of evidence has accumulated implicating defects in the mitochondrial energy generating pathway, oxidative phosphorylation, in a wide variety of degenerative diseases including myopathy and cardiomyopathy. Most classes of pathogenic mitochondrial DNA mutations affect the heart, in association with a variety of of her clinical manifestations that can include skeletal muscle, the central nervous system (including eye), the endocrine system, and the renal system. To better understand the pathophysiologic basis of: mitochondrial diseases and their role in myopathy and cardiomyopathy, several mouse models of mitochondrial disease have been prepared. Mitochondrial DNA mutations from cultured cells have been introduced into mice; nuclear DNA genes involved in mitochondrial energy production and reactive oxygen species detoxification have been genetically inactivated, which resulted in mice with hypertrophic and dilated cardiomyopathy, respectively. Physiologic characterization of these mice has confirmed the importance of decreased mitochondrial energy production, increased mitochondrial reactive oxygen species production, and the mitochondrial initiation of apoptosis in mitochondrial disease. With these insights, new therapeutic approaches for neuromuscular and cardiac disease have been suggested.