中国科学院生物物理研究所李新建小组发现，ABCG2是一种衣康酸排出蛋白，它通过减轻TFEB依赖性溶酶体生物生成来限制抗菌先天免疫能力。相关论文于2024年1月4日在线发表在《细胞—代谢》杂志上。
通过基因筛选，研究人员发现在人和小鼠的巨噬细胞中，衣康酸是通过ATP结合盒转运体G2（ABCG2）以ATP酶依赖的方式从细胞质输出到细胞外空间的。在缺乏ABCG2介导的衣康酸输出的炎症巨噬细胞中，可以观察到转录因子TFEB依赖性溶酶体生物生成和抗菌先天免疫的升高。此外，在鼠伤寒杆菌感染模型中，巨噬细胞中缺乏ABCG2介导的衣康酸输出可促进抗菌先天性免疫防御。
因此，这些研究结果表明，ABCG2介导的衣康酸输出是一种关键的调控机制，它限制了炎性巨噬细胞中依赖于TFEB的溶酶体生物生成和抗菌先天免疫，这意味着阻断衣康酸输出在治疗人类细菌感染方面具有潜在的治疗作用。
据了解，衣康酸是一种代谢物，由线粒体中的顺式乌头酸合成，并被转运到细胞质中，在巨噬细胞中发挥多种调节作用。然而，衣康酸从巨噬细胞中排出的机制仍然未知。
附：英文原文
Title: ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis
Author: Chao Chen, Zhenxing Zhang, Caiyun Liu, Pengkai Sun, Ping Liu, Xinjian Li
Issue&Volume: 2024-01-04
Abstract: Itaconate is a metabolite that synthesized from cis-aconitate in mitochondria and transported into the cytosol to exert multiple regulatoryeffects in macrophages. However, the mechanism by which itaconate exits from macrophagesremains unknown. Using a genetic screen, we reveal that itaconate is exported fromcytosol to extracellular space by ATP-binding cassette transporter G2 (ABCG2) in anATPase-dependent manner in human and mouse macrophages. Elevation of transcriptionfactor TFEB-dependent lysosomal biogenesis and antibacterial innate immunity are observedin inflammatory macrophages with deficiency of ABCG2-mediated itaconate export. Furthermore,deficiency of ABCG2-mediated itaconate export in macrophages promotes antibacterialinnate immune defense in a mouse model of S. typhimurium infection. Thus, our findings identify ABCG2-mediated itaconate export as a key regulatorymechanism that limits TFEB-dependent lysosomal biogenesis and antibacterial innateimmunity in inflammatory macrophages, implying the potential therapeutic utility ofblocking itaconate export in treating human bacterial infections.
DOI: 10.1016/j.cmet.2023.12.015
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00465-5
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx
本期文章：《细胞—代谢》：Online/在线发表
