The Stat proteins (signal transducers and activators of transcription) are transcription factors that are activated in response to cytokines. As if Stat3 did not have enough to do, Wegrzyn et al. (see the Perspective by Myers) now find that Stat3 appears to have a distinct function in the mitochondria. Because Stat3 interacts with a component of complex I of the electron transport chain and interferons, which signal through Stat proteins, inhibit mitochondrial function, the authors explored a role for Stat3 in mitochondria. Stat3 was indeed detected in the mitochondria of cultured cells and cells isolated from tissues, and cells lacking Stat3 had inhibited function of the electron transport chain. Mitochondrial function could be restored by expression of Stat3 targeted to the mitochondria, and the traditional transcriptional regulatory function of Stat3 appeared not to be necessary; mutants compromised for transcriptional activation still rescued mitochondrial function.
J. Wegrzyn, R. Potla, Y.-J. Chwae, N. B. V. Sepuri, O. Zhang, T. Koeck, M. Derecka, K. Szczepanek, M. Szelag, A. Gornicka, A. Moh, S. Moghaddas, Q. Chen, S. Bobbili, J. Cichy, J. Dulak, D. P. Baker, A. Wolfman, D. Stuehr, M. O. Hassan, X.-Y. Fu, N. Avadhani, J. I. Drake, P. Fawcett, E. J. Lesnefsky, A. C. Larner, Function of mitochondrial Stat3 in cellular respiration. Science 323, 793–797 (2009). [Abstract] [FullText]