一个古老的线粒体程序根据血红素的可用性调整翻译
一个古老的线粒体程序根据血红素的可用性调整翻译
作者： 小柯机器人 发布时间：2026/8/6 15:31:31
本期文章：《自然》：Online/在线发表
一个古老的线粒体程序根据血红素的可用性调整翻译，这一成果由德国慕尼黑路德维希马克西米利安大学Lucas T. Jae小组经过不懈努力而取得。该研究于2026年8月5日发表于国际一流学术期刊《自然》杂志上。
在这里，该团队发现血红素稀缺是通过OMA1-DELE1轴在线粒体内感知的。机制上，血红素缺乏触发OMA1依赖的线粒体释放DELE1。在细胞质中，DELE1从HRI中释放抑制性血红素，这使得激酶的一个关键紊乱片段得以修饰。该课题组研究人员证明这种传感器-致动器在人体组织中起作用，包括红系祖细胞，并且在进化上保守到无血无脊椎动物，它们早于以血红蛋白为基础的氧运输的出现。值得注意的是，该系统的药理学操作增强了胎儿珠蛋白表达，这是血红蛋白病的中心治疗目标。总之，这些结果揭示了一个原始的哨兵系统，以防止血液相关的毒性从单细胞到有机体规模。
据悉，贫血是全球主要的健康负担，影响着四分之一的人口，每年超过50例。数百万年的健康生命就此消失它由营养性缺铁、遗传性疾病（包括地中海贫血和镰状细胞病）和疟疾引起，其特点是血红蛋白失衡。血红蛋白的活性成分血红蛋白既是必需的，也是有潜在毒性的，因此必须严格控制其水平。然而，监测血红素水平的分子电路仍然不清楚。胞质eIF2α激酶HRI通过在红细胞分化过程中作为翻译的看门人来抵消铁缺乏或地中海贫血中的贫血，这归因于其血液结合能力。
附：英文原文
Title: An ancient mitochondrial program tunes translation to haem availability
Author: Zhang, Xiang, Schuler, Max-Hinderk, etin, Gonca, Eckl, Eva-Maria, Rheinemann, Lara, Mergner, Julia, Steigenberger, Barbara, Pichlmair, Andreas, Jae, Lucas T.
Issue&Volume: 2026-08-05
Abstract: Anaemia is a major global health burden that affects one-quarter of the human population and annually accounts for over 50million years of healthy life lost1. It arises from nutritional iron deficiency, hereditary disorders (including thalassaemia and sickle cell disease) and malaria, and is characterized by haemoglobin imbalances2. Haem—the active component of haemoglobin—is both essential and potentially toxic, which necessitates tight control of levels. However, the molecular circuitry that monitors haem levels remains obscure. The cytosolic eIF2α kinase HRI counteracts anaemia amid iron deficiency or thalassaemia3,4 by acting as a gatekeeper of translation during erythroid differentiation, which has been attributed to its haem-binding ability5. Here we uncover that haem scarcity is sensed inside mitochondria through an OMA1–DELE1 axis. Mechanistically, haem deficiency triggers OMA1-dependent mitochondrial release of DELE1. In the cytosol, DELE1 releases inhibitory haem from HRI, which enables modifications in a crucial disordered segment of the kinase. We demonstrate that this sensor–actuator operates across human tissues, including erythroid progenitors, and is evolutionarily conserved down to bloodless invertebrates, thus predating the emergence of haemoglobin-based oxygen transport. Notably, pharmacological manipulation of this system enhances fetal globin expression—a central therapeutic objective in haemoglobinopathies. Together, these results reveal a primordial sentinel system that safeguards against haem-related toxicity from the single-cell to the organismic scale.
DOI: 10.1038/s41586-026-10885-x
Source: https://www.nature.com/articles/s41586-026-10885-x