Function of Mitochondrial Stat3 in Cellular Respiration

Joanna Wegrzyn; Ramesh Potla; Yong-Joon Chwae; Naresh B. V. Sepuri; Qifang Zhang; Thomas Koeck; Marta Derecka; Karol Szczepanek; Magdalena Szelag; Agnieszka Gornicka; Akira Moh; Shadi Moghaddas; Qun Chen; Santha Bobbili; Joanna Cichy; Jozef Dulak; Darren P. Baker; Alan Wolfman; Dennis Stuehr; Medhat O. Hassan; Xin-Yuan Fu; Narayan Avadhani; Jennifer I. Drake; Paul Fawcett; Edward J. Lesnefsky; Andrew C. Larner

doi:10.1126/science.1164551

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Function of Mitochondrial Stat3 in Cellular Respiration

Joanna Wegrzyn1,2,*,
Ramesh Potla3,*,
Yong-Joon Chwae1,
Naresh B. V. Sepuri4,
Qifang Zhang1,
Thomas Koeck5,
Marta Derecka1,6,
Karol Szczepanek1,6,
Magdalena Szelag1,2,
Agnieszka Gornicka1,7,
Akira Moh8,
Shadi Moghaddas9,
Qun Chen9,
Santha Bobbili1,
Joanna Cichy6,
Jozef Dulak2,
Darren P. Baker10,
Alan Wolfman11,
Dennis Stuehr3,5,
Medhat O. Hassan12,
Xin-Yuan Fu8,
Narayan Avadhani13,
Jennifer I. Drake14,
Paul Fawcett14,
Edward J. Lesnefsky9,15,
Andrew C. Larner1,†

¹ Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
² Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.
³ Department of Biology, Cleveland State University, Cleveland, OH 44114, USA.
⁴ Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
⁵ Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
⁶ Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.
⁷ Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
⁸ Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁹ Division of Cardiology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
¹⁰ BiogenIdec, 14 Cambridge Center, Cambridge, MA 02142, USA.
¹¹ Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
¹² Pathology and Laboratory Medicine Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
¹³ Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁴ Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
¹⁵ Medical Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA.

↵† To whom correspondence should be addressed. E-mail: alarner{at}vcu.edu

↵* These authors contributed equally to this work.

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Science 06 Feb 2009:
Vol. 323, Issue 5915, pp. 793-797
DOI: 10.1126/science.1164551

Joanna Wegrzyn

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

2 Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

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Ramesh Potla

3 Department of Biology, Cleveland State University, Cleveland, OH 44114, USA.

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Yong-Joon Chwae

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

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Naresh B. V. Sepuri

4 Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.

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Qifang Zhang

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

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Thomas Koeck

5 Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

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Marta Derecka

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

6 Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

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Karol Szczepanek

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

6 Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

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Magdalena Szelag

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

2 Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

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Agnieszka Gornicka

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

7 Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.

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Akira Moh

8 Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Shadi Moghaddas

9 Division of Cardiology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

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Qun Chen

9 Division of Cardiology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

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Santha Bobbili

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

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Joanna Cichy

6 Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

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Jozef Dulak

2 Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

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Darren P. Baker

10 BiogenIdec, 14 Cambridge Center, Cambridge, MA 02142, USA.

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Alan Wolfman

11 Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

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Dennis Stuehr

3 Department of Biology, Cleveland State University, Cleveland, OH 44114, USA.

5 Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

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Medhat O. Hassan

12 Pathology and Laboratory Medicine Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA.

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Xin-Yuan Fu

8 Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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Narayan Avadhani

13 Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Jennifer I. Drake

14 Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.

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Paul Fawcett

14 Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.

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Edward J. Lesnefsky

9 Division of Cardiology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

15 Medical Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA.

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Andrew C. Larner

1 Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

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For correspondence: alarner@vcu.edu

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This article has a correction. Please see:

Is corrected by - July 17, 2009

Abstract

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.

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Function of Mitochondrial Stat3 in Cellular Respiration

This article has a correction. Please see:

Abstract

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