Function of Mitochondrial Stat3 in Cellular Respiration
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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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STAT3 can directly regulate mitochondrial function, and Nox2 can modulate mitochondrial activity.
“STAT3 can directly regulate mitochondrial function [97,98], and Nox2 can modulate mitochondrial activity [99][100][101]”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [98]
STAT3 has a specific role in modulating mitochondrial function through mechanisms independent of its nuclear factor function but dependent on phosphorylation at a serine residue.
“STAT3, initially characterized as a nuclear factor that regulates gene expression in response to IL-6 and other cytokines, has been recently found to have a specific role in modulating mitochondrial function through mechanisms independent of its function as a nuclear factor, but dependent on its phosphorylation at a serine residue (412, 445).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [445]
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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
- Venue
- Science
- Published
- 2009-02-06
- Volume
- 323
- Issue
- 5915
- Pages
- 793-797
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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
- Health Sciences › Medicine › Oncology › 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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