Department of Pharmacology, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, P.R. China.
Mol Med Rep. 2019 May;19(5):3367-3375. doi: 10.3892/mmr.2019.10041. Epub 2019 Mar 15.
Leucine zipper/EF‑hand‑containing transmembrane protein 1 (LETM1) has been identified as the gene responsible for Wolf‑Hirschhorn syndrome (WHS), which is characterized by intellectual disability, epilepsy, growth delay and craniofacial dysgenesis. LETM1 is a mitochondrial inner membrane protein that encodes a homolog of the yeast protein Mdm38, which is involved in mitochondrial morphology. In the present review, the importance of LETM1 in WHS and its role within the mitochondrion was explored. LETM1 governs the mitochondrion ion channel and is involved in mitochondrial respiration. Recent studies have reported that LETM1 acts as a mitochondrial Ca2+/H+ antiporter. LETM1 has also been identified as a K+/H+ exchanger, and serves a role in Mg2+ homeostasis. The function of LETM1 in mitochondria regulation is regulated by its binding partners, carboxyl‑terminal modulator protein and mitochondrial ribosomal protein L36. Therefore, we describe the remarkable role of LETM1 in mitochondrial network physiology and its function in mitochondrion‑mediated cell death. In the context of these findings, we suggest that the participation of LETM1 in tumorigenesis through the alteration of cancer metabolism should be investigated. This review provides a comprehensive description of LETM1 function, which is required for mitochondrial homeostasis and cellular viability.
亮氨酸拉链/EF 手包含跨膜蛋白 1（LETM1）已被确定为导致 Wolf-Hirschhorn 综合征（WHS）的基因，WHS 的特征是智力残疾、癫痫、生长迟缓以及颅面发育不全。LETM1 是一种线粒体内膜蛋白，编码酵母蛋白 Mdm38 的同源物，该蛋白参与线粒体形态。在本综述中，探讨了 LETM1 在 WHS 中的重要性及其在线粒体中的作用。LETM1 控制着线粒体离子通道，并参与线粒体呼吸。最近的研究报道称，LETM1 作为线粒体 Ca2+/H+反向转运蛋白发挥作用。LETM1 也被鉴定为 K+/H+交换体，在 Mg2+稳态中发挥作用。其结合伴侣羧基末端调节剂蛋白和线粒体核糖体蛋白 L36 调节 LETM1 在调节线粒体中的功能。因此，我们描述了 LETM1 在调节线粒体网络生理学及其在线粒体介导的细胞死亡中的功能的重要作用。在这些发现的背景下，我们建议通过改变癌症代谢来研究 LETM1 参与肿瘤发生的可能性。本综述全面描述了 LETM1 功能，该功能对于线粒体稳态和细胞活力是必需的。
