细胞非自主血红素获取途径使应激下的红细胞血红蛋白化，这一成果由马里兰大学
该研究团队发现，在应激条件下，红母细胞通过渗透酶血红素反应基因1 （HRG1）输入血红素，该基因定位于质膜并在应激红细胞生成过程中积累，应激红细胞生成是扩大红细胞输出的紧急程序。HRG1缺失损害血红素摄取，抑制终末红细胞分化和导管性贫血。在β-地中海贫血小鼠中，部分HRG1缺失减少了无效的红细胞生成，强调了平衡血红素输入的重要性。这些发现揭示了细胞间血红素共享，并确定HRG1是血红蛋白病的潜在治疗靶点。
研究人员表示，血红素是一种含铁的辅助因子，在线粒体中通过八酶途径合成。虽然细胞被认为是自主管理血红素，但超过1000种蛋白质参与血红素的产生、运输和调节。在终末红细胞分化过程中，线粒体被丢弃，但血红蛋白的产生仍在继续，这意味着细胞非自主血红素供应。
附：英文原文
Title: A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress
Author: Audrey Belot, Andrew Rock, Sohini Dutt, Gia Haemmerle, Amaury Maros, Xiaojing Yuan, Satoru Otsuru, David Bodine, Iqbal Hamza
Issue&Volume: 2026-04-23
Abstract: Heme, an iron-containing cofactor, is synthesized in mitochondria by an eight-enzyme pathway. Although cells were thought to manage heme autonomously, more than 1000 proteins contribute to its production, transport, and regulation. During terminal erythroid differentiation, mitochondria are discarded, yet hemoglobin production continues, which implies a cell-nonautonomous heme supply. We show that, under stress, erythroblasts import heme through the permease heme-responsive gene 1 (HRG1), which localizes to the plasma membrane and accumulates during stress erythropoiesis, the emergency program that expands red cell output. HRG1 loss impaired heme uptake, inhibited terminal erythroid differentiation, and caused anemia. In β-thalassemic mice, partial HRG1 loss reduces ineffective erythropoiesis, underscoring the importance of balanced heme import. These findings reveal intercellular heme sharing and identify HRG1 as a potential therapeutic target in hemoglobinopathies.
DOI: aea0552
Source: https://www.science.org/doi/10.1126/science.aea0552