The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria.
The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria.
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DOI：
10.1083/jcb.151.2.341
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发表时间：
2000-10-16
影响因子：
7.8
通讯作者：
Nunnari, J
中科院分区：
文献类型：
--
作者：
Wong, E D;Wagner, J A;Gorsich, S W;McCaffery, J M;Shaw, J M;Nunnari, J
动力蛋白相关的GT3突变，Mgm1p，已被证明会导致酿酒酵母细胞中的线粒体聚集和线粒体DNA丢失，但Mgm1p在线粒体维护中的确切作用尚不清楚。为了研究MGM1的主要功能，我们表征了新的温度敏感的MGM1等位基因。MGM1细胞中线粒体形态学的检查表明，线粒体网状结构的碎片化是与MGM1功能丧失相关的主要表型，伴随线粒体片段的二次聚集。这种mgm1表型与在FZO1中具有条件突变的细胞中观察到的表型相同，FZO1编码线粒体融合所需的跨膜GT3，这提高了Mgm1p也是融合所需的可能性。与这一想法一致，线粒体融合在交配期间在mgm1细胞中被阻断，并且DNM1的缺失（其编码线粒体分裂所需的动力蛋白相关的GT3）阻断了mgm1细胞中的线粒体片段化。然而，与fzo1细胞相反，mgm1细胞中DNM1的缺失在交配期间恢复线粒体融合。最后的观察结果表明，尽管在mgm1和fzo1细胞之间观察到表型相似性，但MGM1在线粒体融合中不起直接作用。虽然最近报道Mgm1p定位于线粒体外膜，我们的研究表明，Mgm1p定位于线粒体膜间隙。基于我们的本地化数据和Mgm1p的结构同源性发动蛋白，我们假设它的功能在内膜重塑事件。在这种情况下，所观察到的MGM1表型表明，内外膜分裂耦合，MGM1功能的丧失可能会刺激Dnm1p依赖的外膜分裂，导致在结构上不适合融合的线粒体片段的形成。
Mutations in the dynamin-related GTPase, Mgm1p, have been shown to cause mitochondrial aggregation and mitochondrial DNA loss in Saccharomyces cerevisiae cells, but Mgm1p's exact role in mitochondrial maintenance is unclear. To study the primary function of MGM1, we characterized new temperature sensitive MGM1 alleles. Examination of mitochondrial morphology in mgm1 cells indicates that fragmentation of mitochondrial reticuli is the primary phenotype associated with loss of MGM1 function, with secondary aggregation of mitochondrial fragments. This mgm1 phenotype is identical to that observed in cells with a conditional mutation in FZO1, which encodes a transmembrane GTPase required for mitochondrial fusion, raising the possibility that Mgm1p is also required for fusion. Consistent with this idea, mitochondrial fusion is blocked in mgm1 cells during mating, and deletion of DNM1, which encodes a dynamin-related GTPase required for mitochondrial fission, blocks mitochondrial fragmentation in mgm1 cells. However, in contrast to fzo1 cells, deletion of DNM1 in mgm1 cells restores mitochondrial fusion during mating. This last observation indicates that despite the phenotypic similarities observed between mgm1 and fzo1 cells, MGM1 does not play a direct role in mitochondrial fusion. Although Mgm1p was recently reported to localize to the mitochondrial outer membrane, our studies indicate that Mgm1p is localized to the mitochondrial intermembrane space. Based on our localization data and Mgm1p's structural homology to dynamin, we postulate that it functions in inner membrane remodeling events. In this context, the observed mgm1 phenotypes suggest that inner and outer membrane fission is coupled and that loss of MGM1 function may stimulate Dnm1p-dependent outer membrane fission, resulting in the formation of mitochondrial fragments that are structurally incompetent for fusion.