Fis1p and Caf4p, but not Mdv1p, determine the polar localization of Dnm1p clusters on the mitochondrial surface
Fis1p and Caf4p, but not Mdv1p, determine the polar localization of Dnm1p clusters on the mitochondrial surface
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DOI：
10.1242/jcs.03026
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发表时间：
2006-08-01
影响因子：
4
通讯作者：
Jakobs, Stefan
中科院分区：
文献类型：
--
作者：
Schauss, Astrid C.;Bewersdorf, Jorg;Jakobs, Stefan
线粒体分裂机制由大的动力蛋白相关蛋白Dnm1p(在人类中为Drp1/Dlp1)、Fis1p、Mdv1p和Caf4p组成。Dnm1p复合体在线粒体表面的正确组装对于平衡的分裂和融合事件至关重要。利用定量共聚焦显微镜，我们证明了Caf4p对于Dnm1p向线粒体的募集是重要的。线粒体Dnm1p组合体至少可以分为两个形态上可区分的组分。这些组件中的一小部分似乎以Dnm1p-螺旋(或环)的形式存在，它们环绕着小管收缩，很少超过七圈。较大比例的Dnm1p组装主要存在于线粒体小管的一侧。我们表明，这些与线粒体相关的Dnm1p簇中的大多数指向细胞皮质。这种极化取向在FIS1 Delta和CAF4 Delta酵母细胞中被取消，但在mdv1 Delta细胞中和肌动蛋白细胞骨架被破坏后保持。这项研究表明，Caf4p在决定那些不直接参与线粒体分裂过程的Dnm1p簇的极化定位方面发挥着关键作用。
The mitochondrial division machinery consists of the large dynamin-related protein Dnm1p (Drp1/Dlp1 in humans), and Fis1p, Mdv1p and Caf4p. Proper assembly of Dnm1p complexes on the mitochondrial surface is crucial for balanced fission and fusion events. Using quantitative confocal microscopy, we show that Caf4p is important for the recruitment of Dnm1p to the mitochondria. The mitochondrial Dnm1p assemblies can be divided into at least two morphologically distinguishable fractions. A small subset of these assemblies appear to be present as Dnm1p-spirals (or rings) that encircle tubule constrictions, with seldom more than seven turns. A larger fraction of the Dnm1p assemblies is primarily present at one side of the mitochondrial tubules. We show that a majority of these mitochondria-associated Dnm1p clusters point towards the cell cortex. This polarized orientation is abolished in fis1 Delta and caf4 Delta yeast cells, but is maintained in mdv1 Delta cells and after disruption of the actin cytoskeleton. This study suggests that Caf4p plays a key role in determining the polarized localization of those Dnm1p clusters that are not immediately involved in the mitochondrial fission process.