小柯机器人

浙江大学Caiyong Chen团队近期取得重要工作进展，他们研究发现HRG-9的同源物调节血红素从富含血红素隔间中的运输，相关论文于2022年10月19日在线发表于《自然》杂志上。

研究人员发现真核细胞中，血红素反应基因9（HRG-9）（也被称为运输和高尔基组织2（TANGO2））是一种进化保守的血红素伴侣，在把血红素从血红素储存或合成部位运出方面发挥关键作用。秀丽隐杆线虫hrg-9及其同源物hrg-10的缺失导致血红素在溶酶体相关细胞器中的积累，溶酶体是蠕虫的血红素储存场所。同样，酵母和哺乳动物细胞中hrg-9同源物TANGO2的缺失，会导致血红素合成部位线粒体中的血红素过载。

研究人员证明了TANGO2结合血红素并将其从细胞膜转移到载脂蛋白。值得注意的是，同源的Tango2^-/-斑马鱼幼虫会出现多种症状，包括脑病、心律失常和肌病，并在早期发育中死亡。这些缺陷部分类似于人类TANGO2相关的代谢性脑病和心律失常的症状，这是一种由TANGO的突变引起的遗传性疾病。因此，将HRG-9作为细胞内血红素伴侣的鉴定，为探讨TANGO2相关疾病的病因和治疗提供了生物学基础。

据介绍，血红素是一种含铁的四吡咯，对多种细胞和生理过程至关重要。血红素结合蛋白几乎存在于所有的细胞隔室中，但调节细胞内血红素运输和使用的分子机制仍然知之甚少。

附：英文原文

Title: HRG-9 homologues regulate haem trafficking from haem-enriched compartments

Author: Sun, Fengxiu, Zhao, Zhenzhen, Willoughby, Mathilda M., Shen, Shuaiqi, Zhou, Yu, Shao, Yiyan, Kang, Jing, Chen, Yongtian, Chen, Mengying, Yuan, Xiaojing, Hamza, Iqbal, Reddi, Amit R., Chen, Caiyong

Issue&Volume: 2022-10-19

Abstract: Haem is an iron-containing tetrapyrrole that is critical for a variety of cellular and physiological processes1,2,3. Haem binding proteins are present in almost all cellular compartments, but the molecular mechanisms that regulate the transport and use of haem within the cell remain poorly understood2,3. Here we show that haem-responsive gene 9 (HRG-9) (also known as transport and Golgi organization 2 (TANGO2)) is an evolutionarily conserved haem chaperone with a crucial role in trafficking haem out of haem storage or synthesis sites in eukaryotic cells. Loss of Caenorhabditis elegans hrg-9 and its paralogue hrg-10 results in the accumulation of haem in lysosome-related organelles, the haem storage site in worms. Similarly, deletion of the hrg-9 homologue TANGO2 in yeast and mammalian cells induces haem overload in mitochondria, the site of haem synthesis. We demonstrate that TANGO2 binds haem and transfers it from cellular membranes to apo-haemoproteins. Notably, homozygous tango2/ zebrafish larvae develop pleiotropic symptoms including encephalopathy, cardiac arrhythmia and myopathy, and die during early development. These defects partially resemble the symptoms of human TANGO2-related metabolic encephalopathy and arrhythmias, a hereditary disease caused by mutations in TANGO24,5,6,7,8. Thus, the identification of HRG-9 as an intracellular haem chaperone provides a biological basis for exploring the aetiology and treatment of TANGO2-related disorders.

DOI: 10.1038/s41586-022-05347-z

Source: https://www.nature.com/articles/s41586-022-05347-z

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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