Tissue heterogeneity of the mammalian mitochondrial proteome
Tissue heterogeneity of the mammalian mitochondrial proteome
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哺乳动物线粒体蛋白质组的组织异质性
DOI：
10.1152/ajpcell.00108.2006
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发表时间：
2007-02-01
影响因子：
5.5
通讯作者：
Balaban, Robert S.
中科院分区：
文献类型：
--
作者：
Johnson, D. Thor;Harris, Robert A.;Balaban, Robert S.
线粒体的功能主要由核编码蛋白质决定。不同组织对线粒体功能的需求各异，从具有重要生物合成作用（肝脏）到主要以能量代谢为导向的细胞器（心脏）不等。本研究的目的是比较大鼠四种不同组织（脑、肝、心和肾）的线粒体蛋白质组，以深入了解线粒体异质性的程度，并进一步描述整体线粒体蛋白质组的特征。分离线粒体，将其溶解、消化，然后进行定量液相色谱 - 质谱分析。在检测到的16,950种不同的肽段中，鉴定出8,045种蛋白质。1,162种肽段达到了高可信度鉴定阈值，并对其进行了进一步分析。在这1,162种蛋白质中，至少在两种组织之间有1,149种蛋白质的含量存在显著差异（P值和q值<0.05），而有13种蛋白质在任何组织之间均无显著差异。通过查阅文献或借助氨基末端线粒体定位信号确定蛋白质的线粒体来源。根据这些标准，在存在显著差异的蛋白质组中，有382种蛋白质被确认为线粒体蛋白质，493种无法确定为线粒体蛋白质，但也未明确定位于细胞的其他部位。通过氨基末端线粒体定位信号，共有145种蛋白质首次被归入大鼠线粒体蛋白质组。在组织间无显著差异的蛋白质中，有三种被确认为线粒体蛋白质。在存在显著差异的蛋白质中，最值得注意的是组蛋白家族蛋白质以及几种结构蛋白质，包括微管蛋白和中间丝。每个组织的线粒体蛋白质组都具有非常独特的特征，表明其功能侧重点不同。这些数据证实了线粒体由细胞核调控以适应不同组织中特定功能这一观点。
The functionality of the mitochondrion is primarily determined by nuclear encoded proteins. The mitochondrial functional requirements of different tissues vary from a significant biosynthetic role (liver) to a primarily energy metabolism-oriented organelle (heart). The purpose of this study was to compare the mitochondrial proteome from four different tissues of the rat, brain, liver, heart, and kidney, to provide insight into the extent of mitochondrial heterogeneity and to further characterize the overall mitochondrial proteome. Mitochondria were isolated, solubilized, digested, and subjected to quantitative liquid chromatography-mass spectroscopy. Of the 16,950 distinct peptides detected, 8,045 proteins were identified. High-confidence identification threshold was reached by 1,162 peptides, which were further analyzed. Of these 1,162 proteins, 1,149 were significantly different in content (P and q values < 0.05) between at least 2 tissues, whereas 13 were not significantly different between any tissues. Confirmation of the mitochondrial origin of proteins was determined from the literature or via NH2-terminal mitochondrial localization signals. With these criteria, 382 proteins in the significantly different groups were confirmed to be mitochondrial, and 493 could not be confirmed to be mitochondrial but were not definitively localized elsewhere in the cell. A total of 145 proteins were assigned to the rat mitochondrial proteome for the first time via their NH2-terminal mitochondrial localization signals. Among the proteins that were not significantly different between tissues, three were confirmed to be mitochondrial. Most notable of the significantly different proteins were histone family proteins and several structural proteins, including tubulin and intermediate filaments. The mitochondrial proteome from each tissue had very specific characteristics indicative of different functional emphasis. These data confirm the notion that mitochondria are tuned by the nucleus for specific functions in different tissues.