Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity
Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity
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DOI：
10.1016/j.mito.2014.10.005
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发表时间：
2015-01-01
期刊：
影响因子：
4.4
通讯作者：
Pesole, Graziano
中科院分区：
文献类型：
--
作者：
D'Erchia, Anna Maria;Atlante, Anna;Pesole, Graziano
真核细胞包含一群数量和形状可变的线粒体，这些线粒体又包含多个拷贝的微小紧凑基因组（mtDNA），其表达和功能与核基因组严格协调。mtDNA拷贝数在不同的细胞或组织类型之间变化，既响应于总体代谢和生物能量学需求，又作为特定病理条件的结果或原因。在这里，我们提出了一种新的和可靠的方法来评估每个二倍体基因组的有效mtDNA拷贝数，通过调查全外显子组测序（WES）实验获得的脱靶读数。我们还研究了mtDNA拷贝数是否以及如何与线粒体质量，呼吸活性和表达水平相关。分析来自三个年龄和性别匹配的人类个体的六种不同组织，我们发现qPCR估计的mtDNA拷贝数与mtDNA脱靶WES读数频率之间存在高度显著的线性相关性。此外，线粒体DNA拷贝数与通过RNA-Seq测量的线粒体基因表达水平以及线粒体质量和呼吸活性显示出高度显著的相关性。因此，我们的方法使得可行的，在一个大规模的，调查的mtDNA拷贝数在不同的细胞类型，组织和病理条件下，或在特定的治疗。(C)2014 Elsevier B. V.和线粒体研究学会。All rights reserved.
Eukaryotic cells contain a population of mitochondria, variable in number and shape, which in turn contain multiple copies of a tiny compact genome (mtDNA) whose expression and function is strictly coordinated with the nuclear one. mtDNA copy number varies between different cell or tissues types, both in response to overall metabolic and bioenergetics demands and as a consequence or cause of specific pathological conditions. Here we present a novel and reliable methodology to assess the effective mtDNA copy number per diploid genome by investigating off-target reads obtained by whole-exome sequencing (WES) experiments. We also investigate whether and how mtDNA copy number correlates with mitochondrial mass, respiratory activity and expression levels. Analyzing six different tissues from three age- and sex-matched human individuals, we found a highly significant linear correlation between mtDNA copy number estimated by qPCR and the frequency of mtDNA off target WES reads. Furthermore, mtDNA copy number showed highly significant correlation with mitochondrial gene expression levels as measured by RNA-Seq as well as with mitochondrial mass and respiratory activity. Our methodology makes thus feasible, at a large scale, the investigation of mtDNA copy number in diverse cell-types, tissues and pathological conditions or in response to specific treatments. (C) 2014 Elsevier B.V. and Mitochondria Research Society. All rights reserved.