The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation
Open accessAbstract
SUMMARY Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the pro-inflammatory IL-1β-HIF-1α axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions by inhibiting succinate dehydrogenase-mediated oxidation of succinate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1−/− mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages.
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1 retracted
RETRACTED: mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation
Moon, J.-S., Hisata, S., Park, M.-A., DeNicola, G. M., Ryter, S. W., Nakahira, K., & Choi, A. M. K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.046 · Cited by 374
RetractedSuccinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176 · cited 7×
“These observations raise the possibility that the HIF-1a-IL-1b axis is linked to the efficiency and directionality of the electron transport chain in activated macrophages rather than direct signaling through succinate accumulation.”
BackgroundInfluentialIschaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS
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Self-citationMetabolic reprogramming in macrophages and dendritic cells in innate immunity
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Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli
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Self-citationImmune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
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The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021
Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
Mills, E. L., Ryan, D. G., Prag, H. A., Dikovskaya, D., Menon, D., Zaslona, Z., Jedrychowski, M. P., Costa, A. S. H., Higgins, M., Hams, E., et al. (2018) · Nature · doi:10.1038/nature25986 · Cited by 1,885
Inflammation and metabolism in tissue repair and regeneration
Eming, S. A., Wynn, T. A., & Martin, P. (2017) · Science · doi:10.1126/science.aam7928 · Cited by 1,369
Metadata
- Authors
- Lampropoulou, V., Sergushichev, A., Bambouskova, M., Nair, S., Vincent, E. E., Loginicheva, E., Cervantes-Barragan, L., Ma, X., Huang, S. C.-C., Griss, T., Weinheimer, C. J., Khader, S., Randolph, G. J., Pearce, E. J., Jones, R. G., Diwan, A., Diamond, M. S., & Artyomov, M. N.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 24
- Issue
- 1
- Pages
- 158-166
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2460752692
- Cited by
- 1,541
- References
- 22
- FWCI
- 40.88
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Lampropoulou, V., Sergushichev, A., Bambouskova, M., Nair, S., Vincent, E. E., Loginicheva, E., Cervantes-Barragan, L., Ma, X., Huang, S. C.-C., Griss, T., Weinheimer, C. J., Khader, S., Randolph, G. J., Pearce, E. J., Jones, R. G., Diwan, A., Diamond, M. S., & Artyomov, M. N. (2016). Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metabolism. https://doi.org/10.1016/j.cmet.2016.06.004
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