厦门大学Geng Wang和Sipeng Wu共同合作，近期取得重要工作进展。他们研究提出，ANT2作为RNA线粒体跨膜易位的转运子发挥作用。相关研究成果2024年5月29日在线发表于《细胞研究》杂志上。

据介绍，哺乳动物线粒体DNA的双向转录产生能够形成双链RNA（dsRNA）结构的重叠转录本。线粒体dsRNA释放到胞质溶胶中激活dsRNA敏感性免疫信号传导，这是抵御微生物和病毒攻击以及可能癌症的防御机制，但如果不加以控制，可能会导致自身免疫性疾病。

更好地理解这一过程对于这种防御机制的治疗应用，和同源人类疾病的治疗至关重要。线粒体除了输出dsRNA外，还输出和输入多种非编码RNA。然而，人们对这些RNA是如何通过线粒体膜转运的知之甚少。

研究人员提供了直接的证据，表明腺嘌呤核苷酸转位酶-2（ANT2）在线粒体内膜中作为哺乳动物RNA转位酶发挥作用，而不依赖于其ADP/ATP转移酶活性。通过ANT2流出的线粒体dsRNA触发先天免疫。抑制这一过程可以减轻体内炎症，为治疗自身免疫性疾病提供了一种潜在的治疗方法。

附：英文原文

Title:  ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs

Author:Pengcheng Wang, Lixiao Zhang, Siyi Chen, Renjian Li, Peipei Liu, Xiang Li, Hongdi Luo, Yujia Huo, Zhirong Zhang, Yiqi Cai, Xu Liu, Jinliang Huang, Guangkeng Zhou, Zhe Sun, Shanwei Ding, Jiahao Shi, Zizhuo Zhou, Ruoxi Yuan, Liang Liu, Sipeng Wu & Geng Wang.

Issue&Volume:  2024-05-29

Abstract: Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.

DOI：10.1038/s41422-024-00978-5

Source: https://www.nature.com/articles/s41422-024-00978-5