Synchronized mitochondrial and cytosolic translation programs.
Synchronized mitochondrial and cytosolic translation programs.
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DOI：
10.1038/nature18015
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发表时间：
2016-05-26
期刊：
影响因子：
64.8
通讯作者：
Churchman LS
中科院分区：
文献类型：
--
作者：
Couvillion MT;Soto IC;Shipkovenska G;Churchman LS
氧化磷酸化（OXPHOS）是生命的基础。OXPHOS复合物对细胞构成了独特的挑战，因为它们的亚基在两个不同的基因组上编码，即核基因组和线粒体基因组。设计用于研究核/胞质和细菌基因表达的基因组方法尚未广泛应用于线粒体系统;因此，OXPHOS基因的共调节在很大程度上仍未被探索。在这里，我们全球监测线粒体和核基因表达过程中的酿酒酵母线粒体生物合成，当OXPHOS复合物的合成。细胞核和细胞质编码的OXPHOS转录水平不一致地增加。相反，我们观察到，线粒体和胞质翻译是快速和动态调节在一个惊人的同步方式。此外，协调翻译程序通过胞质翻译的复杂和动态控制被单向控制。因此，核基因组仔细地指导线粒体和胞质翻译的协调，以协调每个OXPHOS复合物的及时合成，这代表了塑造线粒体蛋白质组的未被重视的调控层。我们的全细胞基因组分析方法为线粒体生物学的全球基因调控研究奠定了基础。
Oxidative phosphorylation (OXPHOS) is fundamental for life. OXPHOS complexes pose a unique challenge for the cell, because their subunits are encoded on two different genomes, the nuclear genome and the mitochondrial genome. Genomic approaches designed to study nuclear/cytosolic and bacterial gene expression have not been broadly applied to the mitochondrial system; thus the co-regulation of OXPHOS genes remains largely unexplored. Here we globally monitored mitochondrial and nuclear gene expression processes in Saccharomyces cerevisiae during mitochondrial biogenesis, when OXPHOS complexes are synthesized. Nuclear- and mitochondrial-encoded OXPHOS transcript levels do not increase concordantly. Instead, we observe that mitochondrial and cytosolic translation are rapidly and dynamically regulated in a strikingly synchronous fashion. Furthermore, the coordinated translation programs are controlled unidirectionally through the intricate and dynamic control of cytosolic translation. Thus the nuclear genome carefully directs the coordination of mitochondrial and cytosolic translation to orchestrate the timely synthesis of each OXPHOS complex, representing an unappreciated regulatory layer shaping the mitochondrial proteome. Our whole-cell genomic profiling approach establishes a foundation for global gene regulatory studies of mitochondrial biology.