Su Yixun, Huang Xiaomin, Huang Zhangsen, Huang Taida, Xu Yunsheng, Yi Chenju
The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Cell Dev Biol. 2020 Apr 22;8:274. doi: 10.3389/fcell.2020.00274. eCollection 2020.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor (TF) that regulates a variety of biological processes, including a key role in mediating mitochondrial metabolism. It has been shown that STAT3 performs this function by translocating in minute amounts into mitochondria and interacting with mitochondrial proteins and genome. However, whether STAT3 localizes in mitochondria is still up for debate. To decipher the role of mitochondrial STAT3 requires a detailed understanding of its cellular localization. Using Percoll density gradient centrifugation, we surprisingly found that STAT3 is not located in the mitochondrial fraction, but instead, in the mitochondria-associated endoplasmic reticulum membrane (MAM) fraction. This was confirmed by sub-diffraction image analysis of labeled mitochondria in embryonic astrocytes. Also, we find that other TFs that have been previously found to localize in mitochondria are also found instead in the MAM fraction. Our results suggest that STAT3 and other transcriptional factors are, contrary to prior studies, consolidated specifically at MAMs, and further efforts to understand mitochondrial STAT3 function must take into consideration this localization, as the associated functional consequences offer a different interpretation to the questions of STAT3 trafficking and signaling in the mitochondria.
信号转导与转录激活因子3（STAT3）是一种转录因子（TF），可调节多种生物学过程，包括在介导线粒体代谢中起关键作用。研究表明，STAT3通过微量转运到线粒体中并与线粒体蛋白质和基因组相互作用来执行此功能。然而，STAT3是否定位于线粒体仍存在争议。要阐明线粒体STAT3的作用，需要详细了解其细胞定位。通过Percoll密度梯度离心，我们惊讶地发现STAT3并不位于线粒体部分，而是位于线粒体相关内质网膜（MAM）部分。这通过对胚胎星形胶质细胞中标记线粒体的亚衍射图像分析得到证实。此外，我们发现先前发现定位于线粒体的其他转录因子也位于MAM部分。我们的结果表明，与先前的研究相反，STAT3和其他转录因子特异性地聚集在MAM处，并且进一步了解线粒体STAT3功能的努力必须考虑到这种定位，因为相关的功能后果为线粒体中STAT3的运输和信号传导问题提供了不同的解释。
