Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka, 812-8582, Japan.
Department of Life Science, Rikkyo University, Tokyo, 171-8501, Japan.
Commun Biol. 2020 Mar 5;3(1):99. doi: 10.1038/s42003-020-0832-5.
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.
LETM1 是一种位于线粒体内膜的蛋白，对于维持线粒体的形态和嵴结构以及调节线粒体离子稳态是必需的。在这里，我们报告了 LETM1 在嵴结构组织中的作用。我们鉴定了人类 LETM1 的四个氨基酸残基，对于酵母 LETM1 同源物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会破坏包含 LETM1 的蛋白质复合物的正确组装，并阻止由外源性 LETM1 表达引起的线粒体形态的变化。此外，LETM1 蛋白改变体外重建的类脂体的膜的形状，导致在人工脂质体上形成内陷的膜结构。具有丙氨酸取代的 LETM1 突变蛋白不能促进内陷膜结构的形成，这表明 LETM1 在组织线粒体膜形态方面起着基础性的作用。
