BACKGROUND The role of the cytoskeleton in regulating mitochondrial distribution in dividing mammalian cells is poorly understood. We previously demonstrated that mitochondria are transported to the cleavage furrow during cytokinesis in a microtubule-dependent manner. However, the exact subset of spindle microtubules and molecular machinery involved remains unknown. METHODS We employed quantitative imaging techniques and structured illumination microscopy to analyse the spatial and temporal relationship of mitochondria with microtubules and actin of the contractile ring during cytokinesis in HeLa cells. RESULTS Superresolution microscopy revealed that mitochondria were associated with astral microtubules of the mitotic spindle in cytokinetic cells. Dominant-negative mutants of KIF5B, the heavy chain of kinesin-1 motor, and of Miro-1 disrupted mitochondrial transport to the furrow. Live imaging revealed that mitochondrial enrichment at the cell equator occurred simultaneously with the appearance of the contractile ring in cytokinesis. Inhibiting RhoA activity and contractile ring assembly with C3 transferase, caused mitochondrial mislocalisation during division. CONCLUSIONS Taken together, the data suggest a model in which mitochondria are transported by a microtubule-mediated mechanism involving equatorial astral microtubules, Miro-1, and KIF5B to the nascent actomyosin contractile ring in cytokinesis.

中文翻译：

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哺乳动物胞质分裂中的线粒体-细胞骨架关联。

背景技术人们对在分裂的哺乳动物细胞中细胞骨架在调节线粒体分布中的作用了解甚少。我们以前证明线粒体以微管依赖的方式在胞质分裂过程中被运输到卵裂沟。但是，所涉及的纺锤体微管和分子机械的确切子集仍然未知。方法我们采用定量成像技术和结构化照明显微镜技术分析HeLa细胞胞质分裂过程中线粒体与微管和收缩环肌动蛋白的时空关系。结果超分辨率显微镜显示线粒体与细胞动力学细胞中有丝分裂纺锤体的星状微管有关。KIF5B（驱动蛋白1电机的重链）的显性负突变体，和Miro-1破坏了线粒体向犁沟的运输。实时成像显示线粒体在细胞赤道的富集与胞质分裂中收缩环的出现同时发生。用C3转移酶抑制RhoA活性和收缩环装配，在分裂过程中引起线粒体错位。结论综上所述，数据提示了一种模型，其中线粒体通过涉及赤道星形微管，Miro-1和KIF5B的微管介导机制转运至胞质分裂中新生的肌动球蛋白收缩环。用C3转移酶抑制RhoA活性和收缩环装配，在分裂过程中引起线粒体错位。结论综上所述，数据提示了一种模型，其中线粒体通过涉及赤道星形微管，Miro-1和KIF5B的微管介导机制转运至胞质分裂中新生的肌动球蛋白收缩环。用C3转移酶抑制RhoA活性和收缩环装配，在分裂过程中引起线粒体错位。结论综上所述，数据提示了一种模型，其中线粒体通过涉及赤道星形微管，Miro-1和KIF5B的微管介导机制转运至胞质分裂中新生的肌动球蛋白收缩环。