Department of Cellular Biochemistry, University Medical Center Goettingen, D-37073 Goettingen, Germany.
Cluster of Excellence 'Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells' (MBExC), University of Goettingen, Goettingen, Germany.
Nucleic Acids Res. 2020 Dec 16;48(22):12929-12942. doi: 10.1093/nar/gkaa1132.
Translation and ribosome biogenesis in mitochondria require auxiliary factors that ensure rapid and accurate synthesis of mitochondrial proteins. Defects in translation are associated with oxidative phosphorylation deficiency and cause severe human diseases, but the exact roles of mitochondrial translation-associated factors are not known. Here we identify the functions of GTPBP6, a homolog of the bacterial ribosome-recycling factor HflX, in human mitochondria. Similarly to HflX, GTPBP6 facilitates the dissociation of ribosomes in vitro and in vivo. In contrast to HflX, GTPBP6 is also required for the assembly of mitochondrial ribosomes. GTPBP6 ablation leads to accumulation of late assembly intermediate(s) of the large ribosomal subunit containing ribosome biogenesis factors MTERF4, NSUN4, MALSU1 and the GTPases GTPBP5, GTPBP7 and GTPBP10. Our data show that GTPBP6 has a dual function acting in ribosome recycling and biogenesis. These findings contribute to our understanding of large ribosomal subunit assembly as well as ribosome recycling pathway in mitochondria.
线粒体中的翻译和核糖体生物发生需要辅助因子，以确保线粒体蛋白质的快速和准确合成。翻译缺陷与氧化磷酸化缺陷有关，并导致严重的人类疾病，但线粒体翻译相关因子的确切作用尚不清楚。在这里，我们鉴定了 GTPBP6（细菌核糖体再循环因子 HflX 的同源物）在人线粒体中的功能。与 HflX 相似，GTPBP6 促进体外和体内核糖体的解离。与 HflX 不同，GTPBP6 也是线粒体核糖体组装所必需的。GTPBP6 的缺失导致含有核糖体生物发生因子 MTERF4、NSUN4、MALSU1 以及 GTPases GTPBP5、GTPBP7 和 GTPBP10 的大核糖体亚基的晚期组装中间产物的积累。我们的数据表明，GTPBP6 具有在核糖体再循环和生物发生中起作用的双重功能。这些发现有助于我们理解大核糖体亚基的组装以及线粒体中的核糖体再循环途径。
