Department of Biochemistry, University of Hyderabad, India.
Department of Animal Biology, University of Hyderabad, India.
FEBS Lett. 2020 May;594(9):1403-1412. doi: 10.1002/1873-3468.13741. Epub 2020 Feb 18.
STAT3, a transcription factor involved in various physiological and pathological processes, is also present in mitochondria. Mitochondrial STAT3 regulates complex I activity and reactive oxygen species (ROS) production, yet the mechanisms governing its translocation to mitochondria remain poorly understood. In this study, we show that rotenone-induced ROS triggers the Ser727 phosphorylation of STAT3 and its increased mitochondrial localisation. Furthermore, we show that STAT3-depleted cells display increased ROS levels during rotenone treatment. Targeted expression in mitochondria of wild-type STAT3 - but not S727A mutant - lowers ROS levels, indicating the importance of Ser727 phosphorylation, both in rotenone-induced mitochondrial targeting and quenching of ROS levels. Together, our results demonstrate a novel STAT3-mediated feedback mechanism to maintain redox homeostasis during stress.
STAT3 是一种参与多种生理和病理过程的转录因子，也存在于线粒体中。线粒体中的 STAT3 调节复合物 I 的活性和活性氧 (ROS) 的产生，但调控其向线粒体易位的机制仍知之甚少。在这项研究中，我们表明，鱼藤酮诱导的 ROS 触发 STAT3 的 Ser727 磷酸化及其在线粒体中的定位增加。此外，我们还表明，在鱼藤酮处理期间，STAT3 耗竭的细胞显示出增加的 ROS 水平。野生型 STAT3 的靶向表达（而不是 S727A 突变体）降低了 ROS 水平，这表明 Ser727 磷酸化在鱼藤酮诱导的线粒体靶向和 ROS 水平的耗散中都很重要。总之，我们的结果表明了一种新的 STAT3 介导的反馈机制，以在应激期间维持氧化还原平衡。
