Dynamic mitochondrial localisation of STAT3 in the cellular adipogenesis model 3T3-L1
Abstract
A mechanistic relationship exists between protein localisation, activity and cellular differentiation. Understanding the contribution of these molecular mechanisms is required for elucidation of conditions that drive development. Literature suggests non-canonical translocation of the Signal Transducer and Activator of Transcription 3 (STAT3) to the mitochondria contributes to the regulation of the electron transport chain, cellular respiration and reactive oxygen species production. Based on this we investigated the role of mitochondrial STAT3, specifically the serine 727 phosphorylated form, in cellular differentiation using the well-defined mouse adipogenic model 3T3-L1. Relative levels of reactive oxygen species (ROS) and the levels and dynamic localization of pSTAT3S727 were investigated during the initiation of adipogenesis. As a signalling entity, ROS is known to regulate the activation of C/EBPβ to stimulate a critical cascade of events prior to differentiation of 3T3-L1. Results indicate that upon induction of the differentiation programme, relative levels of mitochondrial pSTAT3S727 dramatically decrease in the mitochondria; in contrast the total cellular pSTAT3S727 levels increase. A positive correlation between increasing levels of ROS and dynamic changes in C/EBPβ indicate that mitochondrial STAT3 plays a potential critical role as an initiator of the process. Based on these findings we propose a model for mitochondrial STAT3 as a regulator of ROS in adipogenesis.
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Following induction of differentiation, relative levels of pS-mtSTAT3 are markedly reduced in contrast to elevated levels of total cellular pS-STAT3, leading to increased complex I activity and increased ROS, which accelerates mitotic clonal expansion and increases differentiation efficiency of preadipocytes during adipogenesis.
“following induction of differentiation, relative levels of pS-mtSTAT3 are markedly reduced in contrast to elevated levels of total cellular pS-STAT3”
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 Kramer et al., 2015
Cites
Function of Mitochondrial Stat3 in Cellular Respiration
Wegrzyn, J., Potla, R., Chwae, Y.-J., Sepuri, N. B. V., Zhang, Q., Koeck, T., Derecka, M., Szczepanek, K., Szelag, M., Gornicka, A., et al. (2009) · Science · doi:10.1126/science.1164551 · Cited by 1,014 · see citing works
Ng, I. H. W., Ng, D. C. H., Jans, D. A., & Bogoyevitch, M. A. (2012) · Biochemical Journal · doi:10.1042/bj20120941 · Cited by 63 · cited 1× · see citing works
“One distinct band at approximately 90 kDa was routinely detected when probing for pSTAT3S727 indicating that pSTAT3S727 is potentially the larger a isoform as would be expected [Ng et al., 2012].”
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Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
“Interestingly, following induction of differentiation, relative levels of pS-mtSTAT3 are markedly reduced in contrast to elevated levels of total cellular pS-STAT3 (Kramer et al., 2015), leading to increased complex I activity and resultantly increased ROS, which in turn accelerates mitotic clonal expansion and increa…”
Background
- Authors
- Kramer, A. H., Edkins, A. L., Hoppe, H. C., & Prinsloo, E.
- Affiliations
- Rhodes University (ZA)
- Corresponding author
- Prinsloo, Earl
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2015-05-12
- Volume
- 116
- Issue
- 7
- Pages
- 1232-1240
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2152315340
- Cited by
- 15
- References
- 2
- Citations by year
- 2025: 1 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2015: 1
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- STAT3, mitochondrial translocation, serine 727 phosphorylation, adipogenesis, 3T3-L1 cells, reactive oxygen species, C/EBPβ, cell differentiation, subcellular protein localization, electron transport chain, cellular respiration
- MeSH terms
- Animals, Gene Expression Regulation, Mitochondria, Phosphorylation, Serine, 3T3 Cells, Reactive Oxygen Species, CCAAT-Enhancer-Binding Protein-beta, Adipogenesis, STAT3 Transcription Factor, Mice
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