Nakamura Nobuhiro, Kimura Yasuo, Tokuda Masaki, Honda Shinji, Hirose Shigehisa
Department of Biological Sciences, Tokyo Institute of Technology, 4259-B19 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.
EMBO Rep. 2006 Oct;7(10):1019-22. doi: 10.1038/sj.embor.7400790. Epub 2006 Aug 25.
Mitofusins and Drp1 are key components in mitochondrial membrane fusion and division, but the molecular mechanism underlying the regulation of their activities remains to be clarified. Here, we identified human membrane-associated RING-CH (MARCH)-V as a novel transmembrane protein of the mitochondrial outer membrane. Immunoprecipitation studies demonstrated that MARCH-V interacts with mitofusin 2 (MFN2) and ubiquitinated forms of Drp1. Overexpression of MARCH-V promoted the formation of long tubular mitochondria in a manner that depends on MFN2 activity. By contrast, mutations in the RING finger caused fragmentation of mitochondria. We also show that MARCH-V promotes ubiquitination of Drp1. These results indicate that MARCH-V has a crucial role in the control of mitochondrial morphology by regulating MFN2 and Drp1 activities.
线粒体融合蛋白和动力相关蛋白1（Drp1）是线粒体膜融合与分裂的关键组分，但其活性调控的分子机制仍有待阐明。在此，我们鉴定出人类膜相关RING-CH结构域蛋白5（MARCH-5）是线粒体外膜上一种新的跨膜蛋白。免疫沉淀研究表明，MARCH-5与线粒体融合蛋白2（MFN2）及泛素化形式的Drp1相互作用。MARCH-5的过表达以依赖于MFN2活性的方式促进了长管状线粒体的形成。相比之下，RING结构域的突变导致线粒体碎片化。我们还表明，MARCH-5促进Drp1的泛素化。这些结果表明，MARCH-5通过调节MFN2和Drp1的活性在控制线粒体形态方面发挥关键作用。
