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

作　　者：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 

机构地区：[1]State Key Laboratory for Cellular Stress Biology,Innovation Center for Cell Signaling Network,School of Life Sciences,Xiamen University,Fujian,China [2]School of Life Sciences,Tsinghua University,Beijing,China

出　　处：《Cell Research》2024年第7期504-521,共18页细胞研究（英文版）

基　　金：the Priority Research Program of the Ministry of Science and Technology of China(2017YFA0504600);the National Natural Science Foundation of China(91649103 and 32091159).

摘　　要：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.

关 键 词：FUNCTIONS checked RELEASE 

分 类 号：Q2[生物学—细胞生物学]