Phosphorylation-Induced Motor Shedding Is Required at Mitosis for Proper Distribution and Passive Inheritance of Mitochondria
Phosphorylation-Induced Motor Shedding Is Required at Mitosis for Proper Distribution and Passive Inheritance of Mitochondria
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DOI：
10.1016/j.celrep.2016.07.055
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发表时间：
2016-08-23
期刊：
影响因子：
8.8
通讯作者：
Schwarz, Thomas Lewis
中科院分区：
文献类型：
--
作者：
Chung, Jarom Yan-Ming;Steen, Judith Arunodhaya;Schwarz, Thomas Lewis
间期线粒体与微管结合，有丝分裂的线粒体与纺锤形微管分离，定位于细胞外。在这里，我们表明，这种重新分布不是通过线粒体的主动运输或拴系到细胞骨架来调节的。相反，连接线粒体和微管的动蛋白和动力蛋白从线粒体表面脱落。脱落是由CDK1和Aurora A对线粒体和细胞质靶标的磷酸化驱动的。强迫运动蛋白向有丝分裂线粒体募集马达蛋白来覆盖这种脱落，阻止了它们适当的对称分布，并破坏了线粒体对子细胞的平衡遗传。此外，当结合了动力蛋白的线粒体与有丝分裂纺锤体结合时，它们会阻止细胞周期的进展，并产生双核细胞。因此，我们的结果表明，线粒体表面马达蛋白的调节释放是一个关键的有丝分裂事件。
While interphase mitochondria associate with microtubules, mitotic mitochondria dissociate from spindle microtubules and localize in the cell periphery. Here, we show that this redistribution is not mediated by mitochondrial active transport or tethering to the cytoskeleton. Instead, kinesin and dynein, which link mitochondria to microtubules, are shed from the mitochondrial surface. Shedding is driven by phosphorylation of mitochondrial and cytoplasmic targets by CDK1 and Aurora A. Forced recruitment of motor proteins to mitotic mitochondria to override this shedding prevents their proper symmetrical distribution and disrupts the balanced inheritance of mitochondria to daughter cells. Moreover, when mitochondria with bound dynein bind to the mitotic spindle, they arrest cell-cycle progression and produce binucleate cells. Thus, our results show that the regulated release of motor proteins from the mitochondrial surface is a critical mitotic event.