Spatial colocalization and functional link of purinosomes with mitochondria.
Spatial colocalization and functional link of purinosomes with mitochondria.
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DOI：
10.1126/science.aac6054
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发表时间：
2016-02-12
期刊：
影响因子：
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通讯作者：
Benkovic SJ
中科院分区：
文献类型：
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作者：
French JB;Jones SA;Deng H;Pedley AM;Kim D;Chan CY;Hu H;Pugh RJ;Zhao H;Zhang Y;Huang TJ;Fang Y;Zhuang X;Benkovic SJ
嘌呤生物合成酶组织成动态的细胞体，称为嘌呤体。关于这些结构的时空控制知之甚少。使用超分辨率显微镜，我们证明了嘌呤体与线粒体共定位，这些结果得到了支持的分离嘌呤体酶与线粒体。此外，含有嘌呤体的细胞的数量响应于线粒体功能和代谢的失调。为了探索细胞内信号传导的作用，我们使用无标记测定法进行了激酶组筛选，并鉴定了mTOR影响嘌呤体组装。mTOR抑制破坏嘌呤体-线粒体共定位并抑制由线粒体失调刺激的嘌呤体形成。总的来说，我们的数据表明，mTOR介导的连接之间的嘌呤体和线粒体，并提出了一个一般的方法，mTOR调节核苷酸代谢的时空控制蛋白质协会。
Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria. Moreover, the number of purinosome containing cells responded to dysregulation of mitochondrial function and metabolism. To explore the role of intracellular signaling, we performed a kinome screen using a label-free assay and identified that mTOR influenced purinosome assembly. mTOR inhibition disrupted purinosome-mitochondria colocalization and suppressed purinosome formation stimulated by mitochondria dysregulation. Collectively, our data suggests an mTOR-mediated link between purinosomes and mitochondria and suggests a general means by which mTOR regulates nucleotide metabolism by spatiotemporal control over protein association.