Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Protein Pept Lett. 2021;28(4):382-387. doi: 10.2174/0929866527666201002150316.
Transmembrane protein 166 (TMEM166) is a lysosomal/endoplasmic reticulum (ER)-associated protein found in different species where it functions as a regulator of programmed cell death through autophagy and apoptosis. It is expressed in a variety of normal tissues and organs, and it is involved in a wide variety of physiological and pathological processes, including cancers, infection, autoimmune diseases, and neurodegenerative diseases. Previous studies indicated that TMEM166 is associated with autophagosomal membrane development. TMEM166 can cause lysosomal membrane permeabilization (LMP) leading to the release of proteolytic enzymes, e.g., cathepsins, that may cause potential mitochondrial membrane damage, which triggers several autophagic and apoptotic events. A low level of TMEM166 expression is also found in tumors, while high level of TMEM166 is found in brain ischemia. In addition, loss of TMEM166 leads to impaired NSC self-renewal and differentiation along with a decrease in autophagy. These findings offer a comprehensive understanding of the pathways involved in the role of TMEM166 in programmed cell death and treatment of various diseases.
跨膜蛋白 166（TMEM166）是一种存在于不同物种中的溶酶体/内质网（ER）相关蛋白，它作为自噬和细胞凋亡程序性细胞死亡的调节剂发挥作用。它在多种正常组织和器官中表达，并参与广泛的生理和病理过程，包括癌症、感染、自身免疫性疾病和神经退行性疾病。先前的研究表明，TMEM166 与自噬体膜的发育有关。TMEM166 可引起溶酶体膜通透性（LMP），导致蛋白酶（例如组织蛋白酶）的释放，这些蛋白酶可能导致潜在的线粒体膜损伤，从而引发几种自噬和凋亡事件。在肿瘤中也发现 TMEM166 的表达水平较低，而在脑缺血中发现 TMEM166 的表达水平较高。此外，TMEM166 的缺失导致神经干细胞自我更新和分化受损，同时自噬减少。这些发现为 TMEM166 在程序性细胞死亡和治疗各种疾病中的作用所涉及的途径提供了全面的理解。
