The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain
The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain
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DOI：
10.1038/s42003-020-0832-5
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发表时间：
2020-03
影响因子：
5.9
通讯作者：
Seiko Nakamura;Aiko Matsui;Shiori Akabane;Y. Tamura;Azumi Hatano;Yuriko Miyano;H. Omote;M. Kajikawa;K. Maenaka;Y. Moriyama;T. Endo;T. Oka
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文献类型：
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作者：
Seiko Nakamura;Aiko Matsui;Shiori Akabane;Y. Tamura;Azumi Hatano;Yuriko Miyano;H. Omote;M. Kajikawa;K. Maenaka;Y. Moriyama;T. Endo;T. Oka
LETM 1是维持线粒体形态和嵴结构所需的线粒体内膜蛋白，并调节线粒体离子稳态。在这里，我们报告的作用，LETM 1在组织的嵴结构。我们确定了人LETM 1的四个氨基酸残基，这四个氨基酸残基对于由酵母LETM 1直向同源基因缺失引起的生长缺陷的互补是至关重要的。用丙氨酸取代氨基酸残基破坏了含有LETM 1的蛋白质复合物的正确组装，并防止了由外源性LETM 1表达诱导的线粒体形态的变化。此外，LETM 1蛋白改变了体外重构的脂蛋白体的膜的形状，导致在人工脂质体上形成内陷的膜结构。丙氨酸取代的LETM 1突变蛋白不能促进内陷膜结构的形成，这表明LETM 1在线粒体膜形态的组织中起着重要作用。
LETM1 is a mitochondrial inner membrane protein that is required for maintaining the mitochondrial morphology and cristae structures, and regulates mitochondrial ion homeostasis. Here we report a role of LETM1 in the organization of cristae structures. We identified four amino acid residues of human LETM1 that are crucial for complementation of the growth deficiency caused by gene deletion of a yeast LETM1 orthologue. Substituting amino acid residues with alanine disrupts the correct assembly of a protein complex containing LETM1 and prevents changes in the mitochondrial morphology induced by exogenous LETM1 expression. Moreover, the LETM1 protein changes the shapes of the membranes of in vitro-reconstituted proteoliposomes, leading to the formation of invaginated membrane structures on artificial liposomes. LETM1 mutant proteins with alanine substitutions fail to facilitate the formation of invaginated membrane structures, suggesting that LETM1 plays a fundamental role in the organization of mitochondrial membrane morphology.