Outer membrane protein functions as integrator of protein import and DNA inheritance in mitochondria
Outer membrane protein functions as integrator of protein import and DNA inheritance in mitochondria
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DOI：
10.1073/pnas.1605497113
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发表时间：
2016-08-02
影响因子：
11.1
通讯作者：
Schneider, Andre
中科院分区：
文献类型：
--
作者：
Kaser, Sandro;Oeljeklaus, Silke;Schneider, Andre
锥虫是最早分化的具有完全功能的线粒体的真核生物之一。pATOM 36是锥虫特异性必需线粒体外膜蛋白，其与蛋白质输入有关。通过消融pATOM 36和体外试验诱导的线粒体蛋白质组的变化表明，pATOM 36是组装外膜古老易位酶（ATOM）所必需的，ATOM是其他生物体中TOM复合物的功能类似物。相互下拉实验和免疫荧光分析表明，一部分的pATOM 36相互作用和共定位与TAC 65，以前未表征的三重附着复合物（TAC）的基本组成部分。TAC将单单位线粒体基因组连接到鞭毛的基体，并介导复制的线粒体基因组的分离。RNAi实验表明，pATOM 36，符合其双重定位，不仅是必不可少的ATOM复合物的组装，也是分离的复制线粒体基因组。然而，这两种功能是不同的，因为缺少75个C-末端氨基酸的截短形式的pATOM 36可以拯救动质体DNA错误分离，但不能拯救ATOM复合物组装的缺乏。因此，pATOM 36具有双重功能，并整合线粒体蛋白质输入与线粒体DNA遗传。
Trypanosomatids are one of the earliest diverging eukaryotes that have fully functional mitochondria. pATOM36 is a trypanosomatid-specific essential mitochondrial outer membrane protein that has been implicated in protein import. Changes in the mitochondrial proteome induced by ablation of pATOM36 and in vitro assays show that pATOM36 is required for the assembly of the archaic translocase of the outer membrane (ATOM), the functional analog of the TOM complex in other organisms. Reciprocal pull-down experiments and immunofluorescence analyses demonstrate that a fraction of pATOM36 interacts and colocalizes with TAC65, a previously uncharacterized essential component of the tripartite attachment complex (TAC). The TAC links the single-unit mitochondrial genome to the basal body of the flagellum and mediates the segregation of the replicated mitochondrial genomes. RNAi experiments showthat pATOM36, in line with its dual localization, is not only essential for ATOM complex assembly but also for segregation of the replicated mitochondrial genomes. However, the two functions are distinct, as a truncated version of pATOM36 lacking the 75 C-terminal amino acids can rescue kinetoplast DNA missegregation but not the lack of ATOM complex assembly. Thus, pATOM36 has a dual function and integrates mitochondrial protein import with mitochondrial DNA inheritance.