Function of Mitochondrial Stat3 in Cellular Respiration

• Published in: Science (American Association for the Advancement of Science) Vol. 323; no. 5915; pp. 793 - 797
• Main Authors: Wegrzyn, Joanna, Potla, Ramesh, Chwae, Yong-Joon, Sepuri, Naresh B.V, Zhang, Qifang, Koeck, Thomas, Derecka, Marta, Szczepanek, Karol, Szelag, Magdalena, Gornicka, Agnieszka, Moh, Akira, Moghaddas, Shadi, Chen, Qun, Bobbili, Santha, Cichy, Joanna, Dulak, Jozef, Baker, Darren P, Wolfman, Alan, Stuehr, Dennis, Hassan, Medhat O, Fu, Xin-Yuan, Avadhani, Narayan, Drake, Jennifer I, Fawcett, Paul, Lesnefsky, Edward J, Larner, Andrew C
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 06.02.2009; The American Association for the Advancement of Science
• Subjects: Animals; Antibodies; Biochemistry; Biological and medical sciences; Cell Respiration; Cell structures and functions; Cells, Cultured; Cellular biology; Cytochromes; Cytokines; Cytoplasm; Electron transport chain; Electron Transport Complex I - metabolism; Electron Transport Complex II - metabolism; Fundamental and applied biological sciences. Psychology; Genetics; Homeostasis; Liver; Mice; Mitochondria; Mitochondria - metabolism; Mitochondria and cell respiration; Mitochondria, Heart - metabolism; Mitochondria, Liver - metabolism; Mitochondrial Membranes - metabolism; Molecular and cellular biology; Molecular biology; NADH, NADPH Oxidoreductases - metabolism; Oxidases; Oxidative Phosphorylation; Phosphorylation; Precursor Cells, B-Lymphoid - metabolism; Respiration; Serine - metabolism; Signal Transduction; STAT3 Transcription Factor - chemistry; STAT3 Transcription Factor - metabolism; Transcription factors; Electron transport chain; Vertebrata; Mitochondria; Mammalia; Mouse; Rodentia; Transduction factor STAT; Cell respiration
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1164551

Cytokines such as interleukin-6 induce tyrosine and serine phosphorylation of Stat3 that results in activation of Stat3-responsive genes. We provide evidence that Stat3 is present in the mitochondria of cultured cells and primary tissues, including the liver and heart. In Stat3⁻/⁻ cells, the activities of complexes I and II of the electron transport chain (ETC) were significantly decreased. We identified Stat3 mutants that selectively restored the protein's function as a transcription factor or its functions within the ETC. In mice that do not express Stat3 in the heart, there were also selective defects in the activities of complexes I and II of the ETC. These data indicate that Stat3 is required for optimal function of the ETC, which may allow it to orchestrate responses to cellular homeostasis.