The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Mitochondrial complex III is essential for suppressive function of regulatory T cells
Open accessAbstract
Regulatory T cells (Treg cells), a distinct subset of CD4+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis1,2. Recent studies have demonstrated that Treg cells exhibit a unique metabolic profile, characterized by an increase in mitochondrial metabolism relative to other CD4+ effector subsets3,4. Furthermore, the Treg cell lineage-defining transcription factor, Foxp3, has been shown to promote respiration5,6; however, it remains unknown whether the mitochondrial respiratory chain is required for the T cell-suppression capacity, stability and survival of Treg cells. Here we report that Treg cell-specific ablation of mitochondrial respiratory chain complex III in mice results in the development of fatal inflammatory disease early in life, without affecting Treg cell number. Mice that lack mitochondrial complex III specifically in Treg cells displayed a loss of T cell-suppression capacity without altering Treg cell proliferation and survival. Treg cells deficient in complex III showed decreased expression of genes associated with Treg function, whereas Foxp3 expression remained stable. Loss of complex III in Treg cells increased DNA methylation as well as the metabolites 2-hydroxyglutarate (2-HG) and succinate that inhibit the ten-eleven translocation (TET) family of DNA demethylases7. Thus, Treg cells require mitochondrial complex III to maintain immune regulatory gene expression and suppressive function. Specific ablation of mitochondrial complex III subunits in Treg cells in mice results in inflammatory disease, altered Treg gene expression and defective Treg function, indicating a key functional role for mitochondrial complex III in Treg cells.
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Mitochondrial TCA cycle metabolites control physiology and disease
Martínez-Reyes, I., & Chandel, N. S. (2020) · Nature Communications · doi:10.1038/s41467-019-13668-3 · Cited by 2,813
Self-citationMitochondrial dynamics in health and disease: mechanisms and potential targets
Chen, W., Zhao, H., & Li, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01547-9 · Cited by 1,306
Metabolic support of tumour-infiltrating regulatory T cells by lactic acid
Watson, M. J., Vignali, P. D. A., Mullett, S. J., Overacre-Delgoffe, A. E., Peralta, R. M., Grebinoski, S., Menk, A. V., Rittenhouse, N. L., DePeaux, K., Whetstone, R. D., et al. (2021) · Nature · doi:10.1038/s41586-020-03045-2 · Cited by 1,259
Metabolic regulation of cell growth and proliferation
Zhu, J., & Thompson, C. B. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0123-5 · Cited by 1,116
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Gao, W., Wang, X., Zhou, Y., Wang, X., & Yu, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01046-3 · Cited by 1,042
Metadata
- Authors
- Weinberg, S. E., Singer, B. D., Steinert, E. M., Martinez, C. A., Mehta, M. M., Martínez-Reyes, I., Gao, P., Helmin, K. A., Abdala-Valencia, H., Sena, L. A., Schumacker, P. T., Turka, L. A., & Chandel, N. S.
- Venue
- Nature
- Published
- 2019-01
- Volume
- 565
- Issue
- 7740
- Pages
- 495-499
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2909014200
- Cited by
- 494
- References
- 40
- FWCI
- 20.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Weinberg, S. E., Singer, B. D., Steinert, E. M., Martinez, C. A., Mehta, M. M., Martínez-Reyes, I., Gao, P., Helmin, K. A., Abdala-Valencia, H., Sena, L. A., Schumacker, P. T., Turka, L. A., & Chandel, N. S. (2019). Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature. https://doi.org/10.1038/s41586-018-0846-z
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