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线粒体基因组分离机制的分子模型。

Molecular model of the mitochondrial genome segregation machinery in .

机构信息

Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland.

Graduate School for Cellular and Biomedical Sciences, University of Bern, CH-3012 Bern, Switzerland.

出版信息

Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1809-E1818. doi: 10.1073/pnas.1716582115. Epub 2018 Feb 6.

Abstract

In almost all eukaryotes, mitochondria maintain their own genome. Despite the discovery more than 50 y ago, still very little is known about how the genome is correctly segregated during cell division. The protozoan parasite contains a single mitochondrion with a singular genome, the kinetoplast DNA (kDNA). Electron microscopy studies revealed the tripartite attachment complex (TAC) to physically connect the kDNA to the basal body of the flagellum and to ensure correct segregation of the mitochondrial genome via the basal bodies movement, during the cell cycle. Using superresolution microscopy, we precisely localize each of the currently known TAC components. We demonstrate that the TAC is assembled in a hierarchical order from the base of the flagellum toward the mitochondrial genome and that the assembly is not dependent on the kDNA itself. Based on the biochemical analysis, the TAC consists of several nonoverlapping subcomplexes, suggesting an overall size of the TAC exceeding 2.8 mDa. We furthermore demonstrate that the TAC is required for correct mitochondrial organelle positioning but not for organelle biogenesis or segregation.

摘要

在几乎所有真核生物中,线粒体都拥有自己的基因组。尽管早在 50 多年前就有了这一发现,但人们对基因组在细胞分裂过程中是如何正确分离的仍然知之甚少。原生动物寄生虫 只有一个线粒体和一个独特的基因组,即动基体 DNA(kDNA)。电子显微镜研究揭示了三联体附着复合物(TAC)通过将 kDNA 与鞭毛的基体物理连接,并通过基体的运动,确保线粒体基因组在细胞周期中的正确分离。使用超分辨率显微镜,我们精确地定位了目前已知的 TAC 组件中的每一个。我们证明 TAC 是从鞭毛的基部到线粒体基因组按层次组装的,并且组装不依赖于 kDNA 本身。基于生化分析,TAC 由几个不重叠的亚基组成,这表明 TAC 的总体大小超过 2.8 MDa。我们进一步证明,TAC 对于线粒体细胞器的正确定位是必需的,但对于细胞器的发生或分离则不是必需的。

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