中山大学苏士成等发现靶向线粒体定位的环状RNA（circRNA） ATP5B调控子（SCAR）通过降低线粒体ROS（mROS）输出减轻非酒精性脂肪性肝炎（NASH）。相关论文发表在2020年9月14日的《细胞》杂志上。
通过NASH患者肝成纤维细胞的circRNA表达谱分析，他们观察到NASH成纤维细胞下调的circRNA的很大一部分是线粒体circRNA。通过构建靶向线粒体的纳米颗粒，他们观察到位于线粒体中的与脂肪性肝炎相关的circRNA SCAR抑制mROS输出和成纤维细胞活化。
由PGC-1α介导的circRNA SCAR与ATP5B结合，并通过阻断CypD-mPTP相互作用而关闭mPTP。脂质超载会通过内质网（ER）应激诱导的CHOP抑制PGC-1α。在体内，靶向circRNA SCAR可减轻高脂饮食引起的肝硬化和胰岛素抵抗。在临床上，circRNA SCAR与脂肪变性到NASH的进展有关。
总的来说，他们确定了一种线粒体circRNA，可驱动炎症发生并充当NASH的治疗靶标。
据了解，线粒体具有自己的基因组，并在免疫代谢疾病中起关键作用。然而，由于缺乏特定的递送系统，位于线粒体的非编码RNA的功能很大程度上未知。
附：英文原文
Title: Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output
Author: Qiyi Zhao, Jiayu Liu, Hong Deng, Ruiying Ma, Jian-You Liao, Huixin Liang, Jingxiong Hu, Jiaqian Li, Zhiyong Guo, Junchao Cai, Xiaoding Xu, Zhiliang Gao, Shicheng Su
Issue&Volume: 2020-09-14
Abstract: Mitochondria, which play central roles in immunometabolic diseases, have their owngenome. However, the functions of mitochondria-located noncoding RNAs are largelyunknown due to the absence of a specific delivery system. By circular RNA (circRNA)expression profile analysis of liver fibroblasts from patients with nonalcoholic steatohepatitis(NASH), we observe that mitochondrial circRNAs account for a considerable fractionof downregulated circRNAs in NASH fibroblasts. By constructing mitochondria-targetingnanoparticles, we observe that Steatohepatitis-associated circRNA ATP5B Regulator(SCAR), which is located in mitochondria, inhibits mitochondrial ROS (mROS) outputand fibroblast activation. circRNA SCAR, mediated by PGC-1α, binds to ATP5B and shutsdown mPTP by blocking CypD-mPTP interaction. Lipid overload inhibits PGC-1α by endoplasmicreticulum (ER) stress-induced CHOP. In vivo, targeting circRNA SCAR alleviates high fat diet-induced cirrhosis and insulin resistance.Clinically, circRNA SCAR is associated with steatosis-to-NASH progression. Collectively,we identify a mitochondrial circRNA that drives metaflammation and serves as a therapeutictarget for NASH.
DOI: 10.1016/j.cell.2020.08.009
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31000-X