Integrated transcriptome analysis across mitochondrial disease etiologies and tissues improves understanding of common cellular adaptations to respiratory chain dysfunction.
Integrated transcriptome analysis across mitochondrial disease etiologies and tissues improves understanding of common cellular adaptations to respiratory chain dysfunction.
复制标题
跨线粒体疾病病因和组织的综合转录组分析提高了对呼吸链功能障碍的常见细胞适应性的理解。
DOI：
10.1016/j.biocel.2014.02.012
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发表时间：
2014-05
影响因子：
4
通讯作者：
Falk, Marni J.
中科院分区：
文献类型：
--
作者：
Zhang, Zhe;Falk, Marni J.
线粒体疾病是一种异质性的、多系统的疾病，对其机制的理解是有限的。为了研究初级呼吸链功能障碍对全球基因表达和途径调控的共同下游影响，我们重新分析了所有公开发表的关于遗传疾病、急性病理生理过程或环境毒素引起的呼吸功能障碍的转录组数据。提供了转录组数据的生物信息学处理的一般概述，以揭示体内和体外对线粒体功能障碍的适应的生物学见解，并讨论了各种独立的细胞、动物和人类组织研究的具体例子。为了促进社区今后集中挖掘这些数据的努力，所有重新分析的转录组数据集都存放在一个可供公众访问的中央网络档案中。我们自己对这些数据的综合荟萃分析发现，在不同的线粒体疾病病因、模型和组织类型中，有几个常见的失调基因。总体而言，转录组分析为研究细胞对线粒体疾病的适应性提供了有用的手段。
Mitochondrial diseases are heterogeneous, multi-systemic disorders for which mechanistic understanding is limited. To investigate common downstream effects of primary respiratory chain dysfunction on global gene expression and pathway regulation, we reanalyzed transcriptome datasets from all publicly available studies of respiratory dysfunction resulting from genetic disorders, acute pathophysiologic processes, or environmental toxins. A general overview is provided of the bioinformatic processing of transcriptome data to uncover biological insights into in vivo and in vitro adaptations to mitochondrial dysfunction, with specific examples discussed from a variety of independent cell, animal, and human tissue studies. To facilitate future community efforts to cohesively mine these data, all reanalyzed transcriptome datasets were deposited into a publicly-accessible central web archive. Our own integrated meta-analysis of these data identified several commonly dysregulated genes across diverse mitochondrial disease etiologies, models, and tissue types. Overall, transcriptome analyses provide a useful means to survey cellular adaptation to mitochondrial diseases.
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