All mitochondria import >95% of their proteins from the cytosol. This process is mediated by protein translocases in the mitochondrial membranes, whose subunits are generally highly conserved. Most eukaryotes have two inner membrane protein translocases (TIMs) that are specialized to import either presequence-containing or mitochondrial carrier proteins. In contrast, the parasitic protozoan Trypanosoma brucei has a single TIM complex consisting of one conserved and five unique subunits. Here, we identify candidates for new subunits of the TIM or the presequence translocase-associated motor (PAM) using a protein–protein interaction network of previously characterized TIM and PAM subunits. This analysis reveals that the trypanosomal TIM complex contains an additional trypanosomatid-specific subunit, designated TbTim15. TbTim15 is associated with the TIM complex, lacks transmembrane domains, and localizes to the intermembrane space. TbTim15 is essential for procyclic and bloodstream forms of trypanosomes. It contains two twin CX₉C motifs and mediates import of both presequence-containing and mitochondrial carrier proteins. While the precise function of TbTim15 in mitochondrial protein import is unknown, our results are consistent with the notion that it may function as an import receptor for the non-canonical trypanosomal TIM complex.

中文翻译：

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膜间定位的 TbTim15 是锥虫单个线粒体内膜蛋白转位酶的重要亚基


所有线粒体 >95% 的蛋白质都从细胞质中导入。该过程由线粒体膜中的蛋白质转位酶介导，其亚基通常高度保守。大多数真核生物都有两种内膜蛋白转位酶 (TIM)，专门用于导入含有前序列的蛋白或线粒体载体蛋白。相比之下，寄生原生动物布氏锥虫有一个单一的 TIM 复合体，由一个保守的亚基和五个独特的亚基组成。在这里，我们使用先前表征的 TIM 和 PAM 亚基的蛋白质-蛋白质相互作用网络来确定 TIM 或前序列易位酶相关运动 (PAM) 新亚基的候选者。该分析表明锥虫 TIM 复合体包含一个额外的锥虫特异性亚基，命名为 TbTim15。 TbTim15 与 TIM 复合物相关，缺乏跨膜结构域，并且定位于膜间隙。 TbTim15 对于锥虫的前循环和血流形式至关重要。它包含两个孪生 CX ₉ C 基序，并介导包含前序列和线粒体载体蛋白的输入。虽然 TbTim15 在线粒体蛋白输入中的精确功能尚不清楚，但我们的结果与它可能作为非经典锥虫 TIM 复合物的输入受体的概念是一致的。