Mouse models of mitochondrial complex I dysfunction.
Mouse models of mitochondrial complex I dysfunction.
复制标题
线粒体复合物 I 功能障碍的小鼠模型。
DOI：
10.1016/j.biocel.2012.08.009
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Pinkert,CarlA
中科院分区：
文献类型：
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作者：
Irwin,MichaelH;Parameshwaran,Kodeeswaran;Pinkert,CarlA
线粒体疾病通常影响具有高能量需求的细胞，并且似乎最深刻地影响具有局部高能量需求的兴奋性细胞，例如神经元和心脏和骨骼肌细胞。哺乳动物线粒体呼吸链的复合物I是非常大的45个亚基的酶，并且复合物I的功能缺陷是氧化磷酸化（OXPHOS）障碍的最常见的原因。复合物I的损伤导致细胞能量产生减少，并导致多种人类脑病、肌病和心肌病。复合物I缺陷可能由编码复合物I亚单位的7个线粒体或38个核基因中的任一个突变引起，或者由影响复合物I组装或功能的各种其他核基因中的突变引起。为了更好地了解复合物I在健康和疾病中的作用，以及评估线粒体疾病的潜在疗法，需要忠实地模拟人类复合物I障碍的小鼠模型。在这篇综述中，我们讨论了现有的小鼠模型的线粒体复合物I功能障碍，重点是那些与人类线粒体疾病的相似之处。我们还讨论了一些值得注意的小鼠遗传模型，其中复合物I基因没有被破坏，但观察到复合物I功能障碍，沿着一些更流行的化合物，抑制复合物I功能，并用于模拟小鼠复合物I缺乏症。这篇文章是一个定向问题的一部分，题为：生物能量功能障碍，适应和治疗。
Diseases of the mitochondria generally affect cells with high-energy demand, and appear to most profoundly affect excitatory cells that have localized high energy requirements, such as neurons and cardiac and skeletal muscle cells. Complex I of the mammalian mitochondrial respiratory chain is a very large, 45 subunit enzyme, and functional deficiency of complex I is the most frequently observed cause of oxidative phosphorylation (OXPHOS) disorders. Impairment of complex I results in decreased cellular energy production and is responsible for a variety of human encephalopathies, myopathies and cardiomyopathies. Complex I deficiency may be caused by mutations in any of the seven mitochondrial or 38 nuclear genes that encode complex I subunits or by mutations in various other nuclear genes that affect complex I assembly or function. Mouse models that faithfully mimic human complex I disorders are needed to better understand the role of complex I in health and disease and for evaluation of potential therapies for mitochondrial diseases. In this review we discuss existing mouse models of mitochondrial complex I dysfunction, focusing on those with similarities to human mitochondrial disorders. We also discuss some of the noteworthy murine genetic models in which complex I genes are not disrupted, but complex I dysfunction is observed, along with some of the more popular chemical compounds that inhibit complex I function and are useful for modeling complex I deficiency in mice. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.