據(jù)美國物理學家組織網(wǎng)日前報道,，北卡羅來納大學和杜克大學的科學家經(jīng)數(shù)年來對細胞分裂的合作研究，為諸如帕金森癥,、阿爾茨海默癥等神經(jīng)退行性疾病乃至某些癌癥的研究提供了新的視角,。相關論文發(fā)表在最新一期《自然—細胞生物學》雜志上。
線粒體被稱為細胞的“發(fā)電廠”,，它們能產(chǎn)生三磷酸腺苷（ATP）,，而這是細胞的化學能來源。細胞繁殖和裂變若要保持一個健康的軌道,，線粒體必須在有絲分裂過程中,，以以一定比例被重新分配到子代細胞中。這個細胞分裂過程非常重要,。
研究人員發(fā)現(xiàn),，一種與Ras基因相關的蛋白質RalA，與幾種不同類型的癌癥有關,，它恰好聚集在線粒體細胞內,。當RalA蛋白質和Aurora-A蛋白質共存于線粒體細胞時，它們的相互作用會導致線粒體在細胞分裂中出現(xiàn)異常,。
研究小組對這些出現(xiàn)異常的線粒體進行研究后發(fā)現(xiàn),，在調節(jié)細胞分裂過程里，線粒體分配的蛋白質信號鏈中,，RalA蛋白質處于起點位置,。如果這些蛋白質被破壞掉，線粒體在有絲分裂中不能恰當?shù)亓炎?，同時也不能在子代細胞中成比例地分配,。這樣的結果之一就是，細胞中ATP的水平下降，導致細胞代謝異常,。
考克斯博士稱,，他們懷疑神經(jīng)退行性疾病和一些癌癥等與潛在的細胞新陳代謝有關，下一步將通過比較一般的細胞與線粒體裂變和重新融合被破壞的細胞,，研究細胞的新陳代謝,。(生物谷 Bioon.com)
doi:10.1038/ncb2310
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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.
