Live imaging reveals the dynamics and regulation of mitochondrial nucleoids during the cell cycle in Fucci2-HeLa cells.

Live imaging reveals the dynamics and regulation of mitochondrial nucleoids during the cell cycle in Fucci2-HeLa cells.
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DOI:
10.1038/s41598-017-10843-8
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发表时间:
2017-09-12
期刊:
影响因子:
4.6
通讯作者:
Sasaki N
Sasaki N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sasaki T;Sato Y;Higashiyama T;Sasaki N

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线粒体DNA(mtDNA)是由称为线粒体类核(mt-nucleoids)的核蛋白复合物组成的,它们是mtDNA复制和传递的关键单位。在人类中,一个细胞中存在数百个线粒体类核。然而,在细胞周期中如何维持大量的线粒体类核仍然是一个谜,因为细胞周期同步化过程会影响mtDNA的复制。在这里,我们分析了在细胞周期中的MT-类核苷酸的维持调节,使用荧光细胞周期指示剂,Fucci 2。具有较高时间分辨率的线粒体类核的实时成像显示在整个细胞周期中线粒体类核频繁附着和分离。TFAM是一种线粒体DNA包装蛋白,它参与了这一动态过程的调节,对维持适当的线粒体类核数量至关重要。线粒体类核数目的增加和线粒体DNA复制的激活都发生在S期。要增加线粒体类核数量,线粒体DNA复制是必要的,而不是核DNA复制。我们建议,这些动态和调节过程中的细胞周期保持几百个线粒体-类核细胞增殖。
Mitochondrial DNA (mtDNA) is organized in nucleoprotein complexes called mitochondrial nucleoids (mt-nucleoids), which are critical units of mtDNA replication and transmission. In humans, several hundreds of mt-nucleoids exist in a cell. However, how numerous mt-nucleoids are maintained during the cell cycle remains elusive, because cell cycle synchronization procedures affect mtDNA replication. Here, we analyzed regulation of the maintenance of mt-nucleoids in the cell cycle, using a fluorescent cell cycle indicator, Fucci2. Live imaging of mt-nucleoids with higher temporal resolution showed frequent attachment and detachment of mt-nucleoids throughout the cell cycle. TFAM, an mtDNA packaging protein, was involved in the regulation of this dynamic process, which was important for maintaining proper mt-nucleoid number. Both an increase in mt-nucleoid number and activation of mtDNA replication occurred during S phase. To increase mt-nucleoid number, mtDNA replication, but not nuclear DNA replication, was necessary. We propose that these dynamic and regulatory processes in the cell cycle maintain several hundred mt-nucleoids in proliferating cells.
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