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Int J Biol Sci 2016; 12(5):532-544. doi:10.7150/ijbs.15153


Mitochondrial Stat3, the Need for Design Thinking

Rui Yang, Mercedes Rincon

Department of Medicine/Immunobiology Program, University of Vermont, Burlington, VT, USA, 05405


Stat3 has been studied extensively as a transcription factor, however the finding that Stat3 also localizes to mitochondria has opened a new area to discover non-classical functions. Here we review the current knowledge of mitochondrial Stat3 as a regulator of the electron transport chain (ETC) and its impact on mitochondrial production of ATP and ROS. We also describe recent findings identifying Stat3 as a regulator of mitochondrial Ca2+ homeostasis through its effect on the ETC. It is becoming evident that these non-classical functions of Stat3 can have a major impact on cancer progression, cardiovascular diseases, and inflammatory diseases. Therefore, mitochondrial Stat3 functions challenge the current design of therapies that solely target Stat3 as a transcription factor and suggest the need for “design thinking,” which leads to the development of novel strategies, to intervene the Stat3 pathway.

Keywords: Stat3

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How to cite this article:
Yang R, Rincon M. Mitochondrial Stat3, the Need for Design Thinking. Int J Biol Sci 2016; 12(5):532-544. doi:10.7150/ijbs.15153. Available from