Institute of Cell Biology, University of Bern, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern CH-3012, Switzerland.
J Cell Sci. 2018 Apr 25;131(8):jcs211730. doi: 10.1242/jcs.211730.
The unicellular parasite harbors one mitochondrial organelle with a singular genome called the kinetoplast DNA (kDNA). The kDNA consists of a network of concatenated minicircles and a few maxicircles that form the kDNA disc. More than 30 proteins involved in kDNA replication have been described. However, several mechanistic questions are only poorly understood. Here, we describe and characterize minicircle replication factor 172 (MiRF172), a novel mitochondrial genome replication factor that is essential for cell growth and kDNA maintenance. By performing super-resolution microscopy, we show that MiRF172 is localized to the kDNA disc, facing the region between the genome and the mitochondrial membranes. We demonstrate that depletion of MiRF172 leads to a loss of minicircles and maxicircles. Detailed analysis suggests that MiRF172 is involved in the reattachment of replicated minicircles to the kDNA disc. Furthermore, we provide evidence that the localization of the replication factor MiRF172 not only depends on the kDNA itself, but also on the mitochondrial genome segregation machinery, suggesting an interaction between the two essential entities.This article has an associated First Person interview with the first author of the paper.
单细胞寄生虫含有一个线粒体细胞器，其基因组称为动基体 DNA（kDNA）。kDNA 由串联的微环和少量的大环组成，形成 kDNA 盘。已经描述了 30 多种参与 kDNA 复制的蛋白质。然而，一些机制问题只是理解得很差。在这里，我们描述并表征了微环复制因子 172（MiRF172），这是一种新型的线粒体基因组复制因子，对细胞生长和 kDNA 维持至关重要。通过进行超分辨率显微镜观察，我们表明 MiRF172 定位于 kDNA 盘，面向基因组和线粒体膜之间的区域。我们证明 MiRF172 的耗竭导致微环和大环的丢失。详细分析表明，MiRF172 参与复制的微环与 kDNA 盘的重新连接。此外，我们提供的证据表明，复制因子 MiRF172 的定位不仅取决于 kDNA 本身，还取决于线粒体基因组分离机制，表明这两个必需实体之间存在相互作用。本文有一篇与论文第一作者的第一人称访谈。
