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Cited by 147Mitochondrial Function and PathologyCytokine Signaling Pathways and InteractionsMetabolism, Diabetes, and Cancer

Mitochondrial Stat3, the need for design thinking

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Yang, Rui, Rincon, Mercedes·2016·International Journal of Biological Sciences
DOI 10.7150/ijbs.15153PMC PMC4807418
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Abstract

Stat3 has been studied extensively as a transcription factor, however the finding that Stat3 also localizes to mitochondria has opened a new area to discover non-classical functions. Here we review the current knowledge of mitochondrial Stat3 as a regulator of the electron transport chain (ETC) and its impact on mitochondrial production of ATP and ROS. We also describe recent findings identifying Stat3 as a regulator of mitochondrial Ca(2+) homeostasis through its effect on the ETC. It is becoming evident that these non-classical functions of Stat3 can have a major impact on cancer progression, cardiovascular diseases, and inflammatory diseases. Therefore, mitochondrial Stat3 functions challenge the current design of therapies that solely target Stat3 as a transcription factor and suggest the need for "design thinking," which leads to the development of novel strategies, to intervene the Stat3 pathway.

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  • IL-6-activated pY-STAT3 transcriptionally induces early production of IL-4 and IL-21 in CD4+ T cells.

    “IL-6–activated pY-STAT3 transcriptionally induces early production of IL-4 and IL-21 in CD4+ T cells”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Yang and Rincon, 2016

    Section 3.3 (page not provided) says that IL-6 promotes IL-4 and IL-21 production in CD4 cells, but attributes transcription-factor STAT3 induction of early expression specifically to IL-21. It does not say that pY-STAT3 transcriptionally induces early IL-4 production; instead, it describes STAT3 sustaining later IL-4 production independently of transcriptional activity. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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References 162 · Cited by 147

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Authors
Yang, R., & Rincon, M.
Affiliations
University of Vermont (US)
ORCID
Yang, Rui
Venue
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Published
2016
Volume
12
Issue
5
Pages
532-544
ISSN
1449-2288 (ISSN-L)
DOI
10.7150/ijbs.15153
PMC
PMC4807418
OpenAlex
W2313930706
Cited by
147
References
162
Citations by year
2026: 14 · 2025: 13 · 2024: 18 · 2023: 11 · 2022: 14 · 2021: 23 · 2020: 13 · 2019: 12 · 2018: 19 · 2017: 7 · 2016: 3
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • International Journal of Biological Sciences (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Association of Immunologists
  • Virginia Commonwealth University
  • National Institutes of Health
  • School of Medicine, Virginia Commonwealth University
  • National Institute of General Medical Sciences (P20GM103496)
  • National Institute of Allergy and Infectious Diseases (R56AI094027, R56AI116255)
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, electron transport chain, mitochondrial ATP production, reactive oxygen species, mitochondrial calcium homeostasis, tumor progression, cardiovascular disease, inflammatory diseases
MeSH terms
Animals, Calcium, Humans, Mitochondria, Reactive Oxygen Species, STAT3 Transcription Factor

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