Fransson Asa, Ruusala Aino, Aspenström Pontus
Ludwig Institute for Cancer Research, Biomedical Center, Box 595, S-751 24 Uppsala, Sweden.
J Biol Chem. 2003 Feb 21;278(8):6495-502. doi: 10.1074/jbc.M208609200. Epub 2002 Dec 12.
The human genomic sequencing effort has revealed the presence of a large number of Rho GTPases encoded by the human genome. Here we report the characterization of a new family of Rho GTPases with atypical features. These proteins, which were called Miro-1 and Miro-2 (for mitochondrial Rho), have tandem GTP-binding domains separated by a linker region containing putative calcium-binding EF hand motifs. Genes encoding Miro-like proteins were found in several eukaryotic organisms from Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster to mammals, indicating that these genes evolved early during evolution. Immunolocalization experiments, in which transfected NIH3T3 and COS 7 cells were stained for ectopically expressed Miro as well as for the endogenous Miro-1 protein, showed that Miro was present in mitochondria. Interestingly, overexpression of a constitutively active mutant of Miro-1 (Miro-1/Val-13) induced an aggregation of the mitochondrial network and resulted in an increased apoptotic rate of the cells expressing activated Miro-1. These data indicate a novel role for Rho-like GTPases in mitochondrial homeostasis and apoptosis.
人类基因组测序工作已揭示人类基因组中存在大量由其编码的Rho GTP酶。在此，我们报告一类具有非典型特征的新型Rho GTP酶家族的特性。这些蛋白质被称为Miro-1和Miro-2（线粒体Rho），具有串联GTP结合结构域，由包含假定钙结合EF手基序的连接区隔开。在从酿酒酵母、秀丽隐杆线虫、黑腹果蝇到哺乳动物的几种真核生物中发现了编码类Miro蛋白的基因，这表明这些基因在进化早期就已演化形成。免疫定位实验中，对转染的NIH3T3和COS 7细胞进行异位表达的Miro以及内源性Miro-1蛋白染色，结果显示Miro存在于线粒体中。有趣的是，Miro-1的组成型活性突变体（Miro-1/Val-13）的过表达诱导了线粒体网络的聚集，并导致表达活化Miro-1的细胞凋亡率增加。这些数据表明Rho样GTP酶在线粒体稳态和凋亡中具有新作用。
