信号传导与转录激活因子3（STAT3）是一种重要的转录因子，是生命必须的，但在包括癌症在内的各种疾病中其活性被破坏。之前人们认为STAT3的生物学完全依赖于其作为转录因子的活性，直到发现了一种线粒体的STAT3池，该池对于正常组织功能和肿瘤发生至关重要。然而，这种线粒体活性的机制仍然不清楚。本研究利用免疫沉淀和质谱技术鉴定到一个包含STAT3、富含亮氨酸五重复与Pentatricopeptide repeat containing (LRPPRC)，和SRA stem-loop交互RNA结合蛋白（SLIRP）的复合物，该复合物对成熟线粒体编码mRNA的稳定性和运输至线粒体核糖体是必需的。此外，我们还展示了该复合物在肺腺癌患者中富集，并且其删除可以抑制肺癌在体内的生长，从而提供了通过特定靶向STAT3的线粒体活性来进行治疗的机会。版权所有© 2023作者。Elsevier出版公司保留所有权利。

Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.