Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nat Cell Biol. 2011 Aug 7;13(9):1108-15. doi: 10.1038/ncb2310.
Mitochondria exist as dynamic interconnected networks that are maintained through a balance of fusion and fission. Equal distribution of mitochondria to daughter cells during mitosis requires fission. Mitotic mitochondrial fission depends on both the relocalization of the large GTPase DRP1 to the outer mitochondrial membrane and phosphorylation of Ser 616 on DRP1 by the mitotic kinase cyclin B-CDK1 (ref. 2). We now report that these processes are mediated by the small Ras-like GTPase RALA and its effector RALBP1 (also known as RLIP76, RLIP1 or RIP1; refs 3, 4). Specifically, the mitotic kinase Aurora A phosphorylates Ser 194 of RALA, relocalizing it to the mitochondria, where it concentrates RALBP1 and DRP1. Furthermore, RALBP1 is associated with cyclin B-CDK1 kinase activity that leads to phosphorylation of DRP1 on Ser 616. Disrupting either RALA or RALBP1 leads to a loss of mitochondrial fission at mitosis, improper segregation of mitochondria during cytokinesis and a decrease in ATP levels and cell number. Thus, the two mitotic kinases Aurora A and cyclin B-CDK1 converge on RALA and RALBP1 to promote mitochondrial fission, the appropriate distribution of mitochondria to daughter cells and ultimately proper mitochondrial function.
线粒体存在于动态相互连接的网络中，通过融合和裂变的平衡来维持。在有丝分裂过程中，线粒体要均等分配给子细胞，这需要发生裂变。有丝分裂过程中线粒体的裂变既依赖于大型 GTP 酶 DRP1 重新定位到线粒体外膜，也依赖于有丝分裂激酶 cyclin B-CDK1 对 DRP1 丝氨酸 616 位的磷酸化（参考文献 2）。我们现在报告，这些过程是由小 Ras 样 GTP 酶 RALA 及其效应物 RALBP1（也称为 RLIP76、RLIP1 或 RIP1；参考文献 3、4）介导的。具体而言，有丝分裂激酶 Aurora A 磷酸化 RALA 的丝氨酸 194 位，使其重新定位到线粒体，在那里它集中 RALBP1 和 DRP1。此外，RALBP1 与 cyclin B-CDK1 激酶活性相关，导致 DRP1 丝氨酸 616 位的磷酸化。无论是 RALA 还是 RALBP1 的缺失都会导致有丝分裂时线粒体裂变的丧失、细胞分裂过程中线粒体的不当分离以及 ATP 水平和细胞数量的减少。因此，两种有丝分裂激酶 Aurora A 和 cyclin B-CDK1 都集中在 RALA 和 RALBP1 上，以促进线粒体裂变、线粒体向子细胞的适当分配以及最终适当的线粒体功能。
