Cited by 1,014Mitochondrial Function and PathologyCytokine Signaling Pathways and InteractionsMetabolism, Diabetes, and Cancer

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Function of Mitochondrial Stat3 in Cellular Respiration

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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.·2009·Science

DOI 10.1126/science.1164551PMC PMC2758306

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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 â/â 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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Authors: Wegrzyn, J., Potla, R., Chwae, Y.-J., Sepuri, N. B. V., Zhang, Q., Koeck, T., Derecka, M., Szczepanek, K., Szelag, M., Gornicka, A., Moh, A., Moghaddas, S., Chen, Q., Bobbili, S., Cichy, J., Dulak, J., Baker, D. P., Wolfman, A., Stuehr, D., Hassan, M. O., Fu, X.-Y., Avadhani, N., Drake, J. I., Fawcett, P., Lesnefsky, E. J., & Larner, A. C.
Affiliations: Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Cleveland State University (US)
Corresponding author: Potla, Ramesh
Larner, Andrew C.
ORCID: Chwae, Yong-Joon
Sepuri, Naresh B. V.
Zhang, Qifang
Koeck, Thomas
Derecka, Marta
Szczepanek, Karol
Chen, Qun
Cichy, Joanna
Stuehr, Dennis
Fu, Xin-Yuan
Avadhani, Narayan
Drake, Jennifer I.
Lesnefsky, Edward J.
Larner, Andrew C.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2009-02-06
Volume: 323
Issue: 5915
Pages: 793-797
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1164551
PMC: PMC2758306
OpenAlex: W2042503285
Cited by: 1,014
References: 14
Citations by year: 2026: 41 · 2025: 37 · 2024: 44 · 2023: 66 · 2022: 65 · 2021: 78 · 2020: 57 · 2019: 62 · 2018: 58 · 2017: 60 · 2016: 54 · 2015: 57 · 2014: 61 · 2013: 62 · 2012: 82
FWCI: 28.42
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
AJOU Open Repository (Ajou University) (submittedVersion)
Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
IUScholarWorks (Indiana University) (submittedVersion)
Funders: National Institute on Aging (P01-AG15885, P01AG015885)
National Cancer Institute (R01CA098924, CA098924)
National Institute of Allergy and Infectious Diseases (R01AI059710)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: STAT3, mitochondrial STAT3, cellular respiration, electron transport chain, complex I, complex II, heart, liver, interleukin-6, cytokine signaling, transcription factors
MeSH terms: Animals, Cells, Cultured, Homeostasis, Mitochondria, Mitochondria, Heart, Mitochondria, Liver, NADH, NADPH Oxidoreductases, Oxidative Phosphorylation, Phosphorylation, Serine, Signal Transduction, Cell Respiration, Electron Transport Complex II, Electron Transport Complex I, STAT3 Transcription Factor, Mitochondrial Membranes, Mice, Precursor Cells, B-Lymphoid

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