據(jù)美國(guó)物理學(xué)家組織網(wǎng)日前報(bào)道,，北卡羅來納大學(xué)和杜克大學(xué)的科學(xué)家經(jīng)數(shù)年來對(duì)細(xì)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(guān)論文發(fā)表在最新一期《自然—細(xì)胞生物學(xué)》雜志上。
線粒體被稱為細(xì)胞的“發(fā)電廠”,，它們能產(chǎn)生三磷酸腺苷（ATP），而這是細(xì)胞的化學(xué)能來源,。細(xì)胞繁殖和裂變?nèi)粢３忠粋€(gè)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(xì)胞中,。這個(gè)細(xì)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(guān)的蛋白質(zhì)RalA,，與幾種不同類型的癌癥有關(guān),，它恰好聚集在線粒體細(xì)胞內(nèi)。當(dāng)RalA蛋白質(zhì)和Aurora-A蛋白質(zhì)共存于線粒體細(xì)胞時(shí),，它們的相互作用會(huì)導(dǎo)致線粒體在細(xì)胞分裂中出現(xiàn)異常,。
研究小組對(duì)這些出現(xiàn)異常的線粒體進(jìn)行研究后發(fā)現(xiàn)，在調(diào)節(jié)細(xì)胞分裂過程里,，線粒體分配的蛋白質(zhì)信號(hào)鏈中,，RalA蛋白質(zhì)處于起點(diǎn)位置。如果這些蛋白質(zhì)被破壞掉,，線粒體在有絲分裂中不能恰當(dāng)?shù)亓炎?，同時(shí)也不能在子代細(xì)胞中成比例地分配。這樣的結(jié)果之一就是,，細(xì)胞中ATP的水平下降,，導(dǎo)致細(xì)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(xì)胞新陳代謝有關(guān),，下一步將通過比較一般的細(xì)胞與線粒體裂變和重新融合被破壞的細(xì)胞，研究細(xì)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.
