The Diverged Trypanosome MICOS Complex as a Hub for Mitochondrial Cristae Shaping and Protein Import
The Diverged Trypanosome MICOS Complex as a Hub for Mitochondrial Cristae Shaping and Protein Import
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DOI：
10.1016/j.cub.2018.09.008
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发表时间：
2018-11-05
期刊：
影响因子：
9.2
通讯作者：
Hashimi, Hassan
中科院分区：
文献类型：
--
作者：
Kaurov, Iosif;Vancova, Marie;Hashimi, Hassan
线粒体接触位点和嵴组织系统（MICOS）是负责嵴形成的多蛋白复合物。尽管嵴存在于所有能够氧化磷酸化的线粒体中，但在真核生物中似乎只有 Mic10 和 Mic60 是保守的。其余 4 或 5 个已知的 MICOS 亚基是后康塔超群所特有的，该超群包括酵母和哺乳动物，它们是唯一对这种复合物进行实验分析的生物体。我们从布氏锥虫中分离出了 MICOS，布氏锥虫是挖掘锥虫超群的成员，与后锥虫有很大不同。我们表明，它是维持典型发掘物的独特盘状嵴所必需的，例如眼虫和动质体，后者包括锥虫。锥虫 MICOS 由 9 个亚基组成，其中大部分对于正常生长至关重要。与 opisthokonts 不同，它包含两个不同的 Mic10 直向同源物和一个非常规的假定 Mic60，该 Mic60 缺乏 mitofilin 结构域。有趣的是，锥虫特有的必需 MICOS 亚基之一称为 TbMic20，它是一种硫氧还蛋白样蛋白，它似乎参与膜间隙蛋白的输入，包括呼吸链复合物组装因子。这一结果表明锥虫 MICOS 协调嵴形状及其膜上参与呼吸的蛋白质的数量，后者通过 TbMic20 的催化活性进行。因此，锥虫 MICOS 使我们能够定义其哪些特征在所有真核生物中都是保守的，并破译那些代表谱系特异性适应的特征。
The mitochondrial contact site and cristae organization system (MICOS) is a multiprotein complex responsible for cristae formation. Even though cristae are found in all mitochondria capable of oxidative phosphorylation, only Mic10 and Mic60 appear to be conserved throughout eukaryotes. The remaining 4 or 5 known MICOS subunits are specific to the supergroup Opisthokonta, which includes yeast and mammals that are the only organisms in which this complex has been analyzed experimentally. We have isolated the MICOS from Trypanosoma brucei, a member of the supergroup Excavata that is profoundly diverged from opisthokonts. We show that it is required for the maintenance of the unique discoidal cristae that typify excavates, such as euglenids and kinetoplastids, the latter of which include trypanosomes. The trypanosome MICOS consists of 9 subunits, most of which are essential for normal growth. Unlike in opisthokonts, it contains two distinct Mic10 orthologs and an unconventional putative Mic60 that lacks a mitofilin domain. Interestingly, one of the essential trypanosomatid-specific MICOS subunits called TbMic20 is a thioredoxin-like protein that appears to be involved in import of intermembrane space proteins, including respiratory chain complex assembly factors. This result points to trypanosome MICOS coordinating cristae shaping and population of its membrane with proteins involved in respiration, the latter via the catalytic activity of TbMic20. Thus, trypanosome MICOS allows us to define which of its features are conserved in all eukaryotes and decipher those that represent lineage-specific adaptations.