据美国物理学家组织网日前报道，北卡罗来纳大学和杜克大学的科学家经数年来对细胞分裂的合作研究，为诸如帕金森症、阿尔茨海默症等神经退行性疾病乃至某些癌症的研究提供了新的视角。相关论文发表在最新一期《自然—细胞生物学》杂志上。
线粒体被称为细胞的“发电厂”，它们能产生三磷酸腺苷（ATP），而这是细胞的化学能来源。细胞繁殖和裂变若要保持一个健康的轨道，线粒体必须在有丝分裂过程中，以以一定比例被重新分配到子代细胞中。这个细胞分裂过程非常重要。
研究人员发现，一种与Ras基因相关的蛋白质RalA，与几种不同类型的癌症有关，它恰好聚集在线粒体细胞内。当RalA蛋白质和Aurora-A蛋白质共存于线粒体细胞时，它们的相互作用会导致线粒体在细胞分裂中出现异常。
研究小组对这些出现异常的线粒体进行研究后发现，在调节细胞分裂过程里，线粒体分配的蛋白质信号链中，RalA蛋白质处于起点位置。如果这些蛋白质被破坏掉，线粒体在有丝分裂中不能恰当地裂变，同时也不能在子代细胞中成比例地分配。这样的结果之一就是，细胞中ATP的水平下降，导致细胞代谢异常。
考克斯博士称，他们怀疑神经退行性疾病和一些癌症等与潜在的细胞新陈代谢有关，下一步将通过比较一般的细胞与线粒体裂变和重新融合被破坏的细胞，研究细胞的新陈代谢。(生物谷 Bioon.com)
doi:10.1038/ncb2310
PMC:
PMID:
RALA and RALBP1 regulate mitochondrial fission at mitosis
David F. Kashatus; Kian-Huat Lim; Donita C. Brady; Nicole L. K. Pershing; Adrienne D. Cox; Christopher M. Counter
Mitochondria exist as dynamic interconnected networks that are maintained through a balance of fusion and fission1. Equal distribution of mitochondria to daughter cells during mitosis requires fission2. 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.
