Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission
Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission
复制标题
DOI：
10.1074/jbc.m607279200
复制
发表时间：
2007-04-13
影响因子：
4.8
通讯作者：
Mihara, Katsuyoshi
中科院分区：
文献类型：
--
作者：
Taguchi, Naoko;Ishihara, Naotada;Mihara, Katsuyoshi
在有丝分裂过程中，细胞器被遗传给子代细胞，而不是膜结构的动态变化。线粒体是动态的实体，经常相互分裂和融合，在这个过程中，动力蛋白相关的GTP酶Drp1是进行分裂反应所必需的。在这项研究中，我们分析了有丝分裂哺乳动物细胞中的线粒体动力学。虽然间期HeLa细胞中的线粒体为长管状网状结构，但在有丝分裂早期，线粒体呈碎裂状，随后在子代细胞中重新形成丝状网状结构。相比之下，在Drp1基因敲除的细胞中，有丝分裂期间管状线粒体结构保持不变，这表明有丝分裂中的线粒体碎裂需要DRp1对线粒体进行分裂。在有丝分裂过程中，Drp1被Ser-585上的CDK1/Cyclin B特异性磷酸化。外源表达非磷酸化突变体Drp1(S585A)导致有丝分裂线粒体断裂减少。这些结果表明，Ser-d585上Drp1的磷酸化促进了有丝分裂细胞中线粒体的分裂。
Organelles are inherited to daughter cells beyond dynamic changes of the membrane structure during mitosis. Mitochondria are dynamic entities, frequently dividing and fusing with each other, during which dynamin-related GTPase Drp1 is required for the fission reaction. In this study, we analyzed mitochondrial dynamics in mitotic mammalian cells. Although mitochondria in interphase HeLa cells are long tubular network structures, they are fragmented in early mitotic phase, and the filamentous network structures are subsequently reformed in the daughter cells. In marked contrast, tubular mitochondrial structures are maintained during mitosis in Drp1 knockdown cells, indicating that the mitochondrial fragmentation in mitosis requires mitochondrial fission by Drp1. Drp1 was specifically phosphorylated in mitosis by Cdk1/cyclin B on Ser-585. Exogenous expression of unphosphorylated mutant Drp1(S585A) led to reduced mitotic mitochondrial fragmentation. These results suggest that phosphorylation of Drp1 on Ser-d585 promotes mitochondrial fission in mitotic cells.