Reprogramming immunity with itaconate: metabolic mechanisms and therapeutic perspectives

Martinez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 2020;11:102. https://doi.org/10.1038/s41467-019-13668-3.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Arnold PK, Finley LWS. Regulation and function of the mammalian Tricarboxylic acid cycle. J Biol Chem. 2023;299:102838. https://doi.org/10.1016/j.jbc.2022.102838.

Article  PubMed  CAS  Google Scholar 

Xia L, Oyang L, Lin J, Tan S, Han Y, Wu N, et al. The cancer metabolic reprogramming and immune response. Mol Cancer. 2021;20:28. https://doi.org/10.1186/s12943-021-01316-8.

Article  PubMed  PubMed Central  Google Scholar 

Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020;368:eaaw5473. https://doi.org/10.1126/science.aaw5473.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Allen CN, Arjona SP, Santerre M, Sawaya BE. Hallmarks of metabolic reprogramming and their role in viral pathogenesis. Viruses. 2022;14:602. https://doi.org/10.3390/v14030602.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fan X, Yang M, Lang Y, Lu S, Kong Z, Gao Y, et al. Mitochondrial metabolic reprogramming in diabetic kidney disease. Cell Death Dis. 2024;15:442. https://doi.org/10.1038/s41419-024-06833-0.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shen T, Wang T. Metabolic reprogramming in COVID-19. Int J Mol Sci. 2021;22:11475. https://doi.org/10.3390/ijms222111475.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Gao J, Zhu Y, Bei Y. Metabolic reprogramming in cardiovascular diseases. J Cardiovasc Transl Res. 2024;17:33–5. https://doi.org/10.1007/s12265-024-10491-0.

Article  PubMed  Google Scholar 

McGettrick A, Bourner L, Dorsey F, O’Neill L. Metabolic messengers: itaconate. Nat Metabolism. 2024;6:1661–67. https://doi.org/10.1038/s42255-024-01092-x.

Article  CAS  Google Scholar 

Baup S. Ueber eine neue Pyrogen-Citronensäure, und Über benennung der Pyrogen‐Säuren Überhaupt. Ann Pharm. 1836;19:29–38. https://doi.org/10.1002/jlac.18360190107.

Article  Google Scholar 

Turner E. Elements of chemistry: including the actual state and prevalent doctrines of the science. Taylor and Walton. 1841.

Berlin NI. Hans krebs: architect of intermediary metabolism 1933–1937. JAMA. 1994;271:1137–38. https://doi.org/10.1001/jama.1994.03510380095054.

Article  Google Scholar 

Ye DY, Noh MH, Moon JH, Milito A, Kim M, Lee JW, et al. Kinetic compartmentalization by unnatural reaction for Itaconate production. Nat Commun. 2022;13:5353. https://doi.org/10.1038/s41467-022-33033-1.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lee CG, Jenkins NA, Gilbert DJ, Copeland NG, O’Brien WE. Cloning and analysis of gene regulation of a novel LPS-inducible cDNA. Immunogenetics. 1995;41:263–70. https://doi.org/10.1007/BF00172150.

Article  PubMed  CAS  Google Scholar 

Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, et al. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing Itaconic acid production. Proc Natl Acad Sci USA. 2013;110:7820–5. https://doi.org/10.1073/pnas.1218599110.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shi X, Zhou H, Wei J, Mo W, Li Q, Lv X. The signaling pathways and therapeutic potential of Itaconate to alleviate inflammation and oxidative stress in inflammatory diseases. Redox Biol. 2022;58:102553. https://doi.org/10.1016/j.redox.2022.102553.

Article  PubMed  PubMed Central  CAS  Google Scholar 

O’Neill LAJ, Artyomov MN. Itaconate: the poster child of metabolic reprogramming in macrophage function. Nat Rev Immunol. 2019;19:273 – 81. https://doi.org/10.1038/s41577-019-0128-5.

Hersch SJ, Navarre WW. The Salmonella LysR family regulator RipR activates the SPI-13-Encoded Itaconate degradation cluster. Infect Immun. 2020;88. https://doi.org/10.1128/IAI.00303-20.

Ki N, Kim J, Jo I, Hyun Y, Ryu S, Ha NC. Isocitrate binds to the Itaconic acid-responsive LysR-type transcriptional regulator RipR in Salmonella pathogenesis. J Biol Chem. 2022;298:102562. https://doi.org/10.1016/j.jbc.2022.102562.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Xie L, Xu Y, Ding X, Liang S, Li D, Fu A, et al. Itaconic acid and dimethyl Itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle. Biomed Pharmacother. 2023;167:115487. https://doi.org/10.1016/j.biopha.2023.115487.

Article  PubMed  CAS  Google Scholar 

Cordes T, Michelucci A, Hiller K. Itaconic acid: the surprising role of an industrial compound as a mammalian antimicrobial metabolite. Annu Rev Nutr. 2015;35:451–73. https://doi.org/10.1146/annurev-nutr-071714-034243.

Article  PubMed  CAS  Google Scholar 

Nemeth B, Doczi J, Csete D, Kacso G, Ravasz D, Adams D, et al. Abolition of mitochondrial substrate-level phosphorylation by Itaconic acid produced by LPS-induced Irg1 expression in cells of murine macrophage lineage. FASEB J. 2016;30:286–300. https://doi.org/10.1096/fj.15-279398.

Article  PubMed  CAS  Google Scholar 

Yang W, Wang Y, Tao K, Li R. Metabolite Itaconate in host immunoregulation and defense. Cell Mol Biol Lett. 2023;28:100. https://doi.org/10.1186/s11658-023-00503-3.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wu R, Chen F, Wang N, Tang D, Kang R. ACOD1 in immunometabolism and disease. Cell Mol Immunol. 2020;17:822–33. https://doi.org/10.1038/s41423-020-0489-5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Cordes T, Metallo CM. Itaconate alters succinate and coenzyme A metabolism via Inhibition of mitochondrial complex II and Methylmalonyl-CoA mutase. Metabolites. 2021;11:117. https://doi.org/10.3390/metabo11020117.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chun HL, Lee SY, Kim K-H, Lee CS, Oh T-J, Park HH. The crystal structure of mouse IRG1 suggests that cis-aconitate decarboxylase has an open and closed conformation. PLoS ONE. 2020;15:e0242383. https://doi.org/10.1371/journal.pone.0242383.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018;556:113–17. https://doi.org/10.1038/nature25986.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Gidon A, Louet C, Rost LM, Bruheim P, Flo TH. The tumor necrosis factor alpha and Interleukin 6 auto-paracrine signaling loop controls Mycobacterium avium infection via induction of IRF1/IRG1 in human primary macrophages. mBio. 2021;12:e0212121. https://doi.org/10.1128/mBio.02121-21.

Article  PubMed  Google Scholar 

Chen F, Lukat P, Iqbal AA, Saile K, Kaever V, van den Heuvel J, et al. Crystal structure of cis-aconitate decarboxylase reveals the impact of naturally occurring human mutations on Itaconate synthesis. Proc Natl Acad Sci USA. 2019;116:20644–54. https://doi.org/10.1073/pnas.1908770116.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Li Y, Gong W, Li W, Liu P, Liu J, Jiang H, et al. The IRG1-Itaconate axis: a regulatory hub for immunity and metabolism in macrophages. Int Rev Immunol. 2023;42:364–78. https://doi.org/10.1080/08830185.2022.2067153.

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