Regulation of mitochondrial dynamics by Aurora A kinase
Regulation of mitochondrial dynamics by Aurora A kinase
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DOI：
10.1101/236612
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
Rhys Grant;A. Abdelbaki;Alessia Bertoldi;M. P. Gavilán;J. Mansfeld;D. Glover;C. Lindon
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文献类型：
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作者：
Rhys Grant;A. Abdelbaki;Alessia Bertoldi;M. P. Gavilán;J. Mansfeld;D. Glover;C. Lindon
Aurora A激酶（AURKA）是有丝分裂的主要调节因子，也是癌症进展的重要驱动因素。AURKA在有丝分裂之外的作用，以及这些作用如何促进癌症进展，目前还不清楚。在这里，我们表明，一部分细胞质AURKA与线粒体，共分馏细胞提取物和相互作用的线粒体蛋白质的相互作用免疫共沉淀。我们还发现线粒体网络的动态对AURKA抑制、耗尽或过表达敏感。这可以解释在RPE 1和U2 OS细胞系中观察到的不同线粒体形态，其显示出非常不同的AURKA表达水平。我们确定的线粒体部分AURKA影响线粒体形态，因为N-末端截短的版本的激酶，不本地化的线粒体不影响线粒体网络。我们确定了一个神秘的线粒体靶向序列在AURKA N-末端，并讨论如何替代构象的蛋白质可能会影响其细胞质的命运。
Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, since an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.