Myo19 ensures symmetric partitioning of mitochondria and coupling of mitochondrial segregation to cell division.
Myo19 ensures symmetric partitioning of mitochondria and coupling of mitochondrial segregation to cell division.
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Myo19 确保线粒体的对称分配以及线粒体分离与细胞分裂的耦合。
DOI：
10.1016/j.cub.2014.09.045
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Baum,Buzz
中科院分区：
文献类型：
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作者：
Rohn,JenniferL;Patel,JignaV;Neumann,Beate;Bulkescher,Jutta;Mchedlishvili,Nunu;McMullan,RachelC;Quintero,OmarA;Ellenberg,Jan;Baum,Buzz
在动物细胞分裂过程中，基于肌动蛋白的环将细胞分裂成两部分。这一过程的问题可能导致染色体错误分离以及细胞质遗传和细胞器分配的缺陷，进而与人类疾病相关[1-3]。尽管人们对染色体分离如何与细胞分裂相结合了解很多，但细胞器在分配为子细胞期间协调其遗传的方式却不太了解。在这里，我们使用高内涵实时成像小干扰 RNA 筛选，将 Myosin-XIX (Myo19) 确定为细胞分裂的新型调节剂。此前，这种基于肌动蛋白的马达被证明可以控制线粒体的间期运动[4]。我们的分析表明，Myo19 确实定位于线粒体，并且其沉默会导致细胞内线粒体分布和分裂时线粒体分配的缺陷。此外，许多 Myo19 RNAi 细胞经历随机分裂失败，这种表型可以通过阻止线粒体裂变的治疗来模拟，并通过减少线粒体融合来挽救，这意味着线粒体可以物理干扰胞质分裂。引人注目的是，使用实时成像，我们还观察到当 Myo19 耗尽的细胞进入后期时，线粒体向纺锤体两极的不适当运动。由于该表型复制了后期肌动蛋白丝急剧丧失的结果，因此这些数据支持一个模型，即基于 Myo19 肌动蛋白的马达有助于控制线粒体运动，以确保它们在分裂过程中忠实分离。线粒体内DNA的存在使得它们的遗传成为对称细胞分裂的一个特别重要的方面。
During animal cell division, an actin-based ring cleaves the cell into two. Problems with this process can cause chromosome missegregation and defects in cytoplasmic inheritance and the partitioning of organelles, which in turn are associated with human diseases [1–3]. Although much is known about how chromosome segregation is coupled to cell division, the way organelles coordinate their inheritance during partitioning to daughter cells is less well understood. Here, using a high-content live-imaging small interfering RNA screen, we identify Myosin-XIX (Myo19) as a novel regulator of cell division. Previously, this actin-based motor was shown to control the interphase movement of mitochondria [4]. Our analysis shows that Myo19 is indeed localized to mitochondria and that its silencing leads to defects in the distribution of mitochondria within cells and in mitochondrial partitioning at division. Furthermore, many Myo19 RNAi cells undergo stochastic division failure—a phenotype that can be mimicked using a treatment that blocks mitochondrial fission and rescued by decreasing mitochondrial fusion, implying that mitochondria can physically interfere with cytokinesis. Strikingly, using live imaging we also observe the inappropriate movement of mitochondria to the poles of spindles in cells depleted for Myo19 as they enter anaphase. Since this phenocopies the results of an acute loss of actin filaments in anaphase, these data support a model whereby the Myo19 actin-based motor helps to control mitochondrial movement to ensure their faithful segregation during division. The presence of DNA within mitochondria makes their inheritance an especially important aspect of symmetrical cell division.