RT Journal Article
SR Electronic
T1 STAT3 localizes in mitochondria-associated ER membranes instead of in mitochondria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.18.880567
DO 10.1101/2019.12.18.880567
A1 Yixun Su
A1 Xiaomin Huang
A1 Zhangsen Huang
A1 Taida Huang
A1 Yunsheng Xu
A1 Chenju Yi
YR 2019
UL http://biorxiv.org/content/early/2019/12/22/2019.12.18.880567.abstract
AB 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.