Phase separation drives the self-assembly of mitochondrial nucleoids for transcriptional modulation
Phase separation drives the self-assembly of mitochondrial nucleoids for transcriptional modulation
复制标题
相分离驱动线粒体核苷的自组装以进行转录调节。
DOI：
10.1038/s41594-021-00671-w
复制
发表时间：
2021-10-28
影响因子：
16.8
通讯作者：
Liu, Xingguo
中科院分区：
文献类型：
--
作者：
Long, Qi;Zhou, Yanshuang;Liu, Xingguo
荧光成像和光漂白后的荧光恢复分析表明，线粒体类核通过线粒体DNA和线粒体转录机器之间的液-液相分离作用形成亚细胞器。线粒体是哺乳动物细胞中唯一的半自主细胞器，拥有一个环形的双链基因组，称为线粒体DNA(MtDNA)。虽然核基因组DNA的紧凑、染色质的区域化和转录受相分离的调节，但线粒体类核是如何组装的，一个高度致密的球形亚细胞器，其功能尚不清楚。在这里，我们在体外组装了线粒体核团，并证明了线粒体转录因子A(TFAM)与线粒体DNA经历了相分离，从而驱动了核团的自组装。此外，类核液滴的形成通过一种特殊的共相分离促进转录机制的招募，这种分离集中了转录起始、延长和终止因子，并保留了底物以促进mtDNA转录。我们提出了一个由相分离驱动的线粒体类核自组装模型，以及一个参与线粒体转录调控的共相分离模式，该模式协调了TFAM在线粒体类核组织和转录中的作用。
Fluorescence imaging and fluorescence recovery after photobleaching assays reveal that the mitochondrial nucleoid forms a suborganelle via liquid-liquid phase separation interactions between mitochondrial DNA and the mitochondrial transcriptional machinery.Mitochondria, the only semiautonomous organelles in mammalian cells, possess a circular, double-stranded genome termed mitochondrial DNA (mtDNA). While nuclear genomic DNA compaction, chromatin compartmentalization and transcription are known to be regulated by phase separation, how the mitochondrial nucleoid, a highly compacted spherical suborganelle, is assembled and functions is unknown. Here we assembled mitochondrial nucleoids in vitro and show that mitochondrial transcription factor A (TFAM) undergoes phase separation with mtDNA to drive nucleoid self-assembly. Moreover, nucleoid droplet formation promotes recruitment of the transcription machinery via a special, co-phase separation that concentrates transcription initiation, elongation and termination factors, and retains substrates to facilitate mtDNA transcription. We propose a model of mitochondrial nucleoid self-assembly driven by phase separation, and a pattern of co-phase separation involved in mitochondrial transcriptional regulation, which orchestrates the roles of TFAM in both mitochondrial nucleoid organization and transcription.