ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast.
ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast.
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DOI：
10.7554/elife.00422
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发表时间：
2013-05-14
期刊：
影响因子：
7.7
通讯作者：
Nunnari J
中科院分区：
文献类型：
--
作者：
Murley A;Lackner LL;Osman C;West M;Voeltz GK;Walter P;Nunnari J
线粒体分裂对于线粒体的分布和功能是重要的。最近的数据表明，ER-线粒体接触标志着线粒体分裂位点，但这些接触的分子基础和功能尚不清楚。在这里，我们表明，在酵母中，ER-线粒体拴系复合物，ERMES，和高度保守的米罗GTdR，Gem 1，在空间和功能上与ER相关的线粒体分裂。Gem 1作为ER-线粒体接触的负调节剂，这是分裂后新产生的线粒体尖端的空间分辨率和分布所需的活性。先前的数据已经证明ERMES定位于活跃复制的线粒体类核的子集。我们发现，线粒体分裂是空间上连接到类核和大多数这些类核分裂前分离，导致其分布到新生成的提示在线粒体网络。因此，我们假设ER相关的分裂用于连接细胞中线粒体和线粒体类核的分布。DOI：http://dx.doi.org/10.7554/eLife.00422.001线粒体产生细胞使用的大部分能量，它们在细胞生长、死亡和分化中也起着关键作用。它们在进化上来源于细菌，并保留了自己的DNA和蛋白质翻译系统，但它们也依赖于细胞的生长和复制。细胞外膜的重要部分与内质网（ER）接触，内质网是合成分泌蛋白质的起点，也是合成脂质和其他细胞器的关键。最近的研究表明，Escheria-ER接触点标志着线粒体分裂的位点，但目前还不清楚这一过程是如何发生的。在这里，Murley等人使用芽殖酵母和模式生物酿酒酵母（Saccharomyces cerevisiae）来表明，在线粒体分裂位点，一种称为ERMES的多蛋白复合物促进了ER-线粒体接触点的形成，而一种进化上保守的酶Gem 1则拮抗这些接触，以帮助线粒体分离。这些接触点被发现与类核（线粒体DNA和蛋白质的复合物）相邻-这一观察表明ER相关的线粒体分裂进化以帮助在新形成的线粒体之间分配类核。本研究还揭示了保守蛋白Gem 1的新作用，并可能导致研究人员重新研究Miro 1/2的功能-高等真核生物中Gem 1的等价物。Miro 1/2被认为连接线粒体和马达蛋白，马达蛋白将线粒体沿着沿着微管运送通过细胞。Miro 1/2的功能障碍降低了线粒体的流动性，Murley等人的工作表明这可能是线粒体和ER之间接触增强的结果。DOI：http://dx.doi.org/10.7554/eLife.00422.002网站
Mitochondrial division is important for mitochondrial distribution and function. Recent data have demonstrated that ER–mitochondria contacts mark mitochondrial division sites, but the molecular basis and functions of these contacts are not understood. Here we show that in yeast, the ER–mitochondria tethering complex, ERMES, and the highly conserved Miro GTPase, Gem1, are spatially and functionally linked to ER-associated mitochondrial division. Gem1 acts as a negative regulator of ER–mitochondria contacts, an activity required for the spatial resolution and distribution of newly generated mitochondrial tips following division. Previous data have demonstrated that ERMES localizes with a subset of actively replicating mitochondrial nucleoids. We show that mitochondrial division is spatially linked to nucleoids and that a majority of these nucleoids segregate prior to division, resulting in their distribution into newly generated tips in the mitochondrial network. Thus, we postulate that ER-associated division serves to link the distribution of mitochondria and mitochondrial nucleoids in cells. DOI: http://dx.doi.org/10.7554/eLife.00422.001 Mitochondria generate most of the energy used by cells, and they also play key roles in cellular growth, death, and differentiation. They are evolutionarily derived from bacteria and have retained their own DNA and protein translation system, but they are also dependent on the cell for their growth and replication. A significant portion of the outer membrane of a mitochondrion is in contact with the endoplasmic reticulum (ER)—an organelle that is the starting point for the synthesis of secreted proteins, and is also critical for the synthesis of lipids and other organelles. Recent work suggests that mitochondria–ER contact points mark sites of mitochondrial division, but it is unclear exactly how this process occurs. Here, Murley et al. use the budding yeast and model organism Saccharomyces cerevisiae to show that at mitochondrial division sites, a multiprotein complex called ERMES promotes the formation of ER–mitochondrial contact points, while an evolutionarily conserved enzyme, Gem1, antagonizes these contacts to aid mitochondrial segregation. The contact points are found adjacent to nucleoids (which are complexes of mitochondrial DNA and proteins)—an observation suggesting that ER-associated mitochondrial division evolved to help distribute nucleoids between newly formed mitochondria. The present study also reveals a novel role for the conserved protein Gem1 and could lead researchers to reinvestigate the functions of Miro1/2—the equivalent of Gem1 in higher eukaryotes. Miro1/2 is thought to connect mitochondria to motor proteins, which transports them through the cell along microtubules. Dysfunction of Miro1/2 reduces the mobility of mitochondria, and the work of Murley et al. suggests that this could be a consequence of enhanced contacts between mitochondria and the ER. DOI: http://dx.doi.org/10.7554/eLife.00422.002