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Mitochondrial ACOD1/IRG1 in Infection and Sterile Inflammation

Overview
Journal J Intensive Med
Specialty Critical Care
Date 2023 Feb 15
PMID 36789185
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Abstract

Immunometabolism is a dynamic process involving the interplay of metabolism and immune response in health and diseases. Increasing evidence suggests that impaired immunometabolism contributes to infectious and inflammatory diseases. In particular, the mitochondrial enzyme aconitate decarboxylase 1 (ACOD1, best known as immunoresponsive gene 1 [IRG1]) is upregulated under various inflammatory conditions and serves as a pivotal regulator of immunometabolism involved in itaconate production, macrophage polarization, inflammasome activation, and oxidative stress. Consequently, the activation of the ACOD1 pathway is implicated in regulating the pathogenic process of sepsis and septic shock, which are part of a clinical syndrome of life-threatening organ failure caused by a dysregulated host response to pathogen infection. In this review, we discuss the latest research advances in ACOD1 expression and function, with particular attention to how the ACOD1-itaconate pathway affects infection and sterile inflammation diseases. These new insights may give us a deeper understanding of the role of immunometabolism in innate immunity.

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References
1.
Ahmed S, Luo L, Namani A, Wang X, Tang X . Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis. 2016; 1863(2):585-597. DOI: 10.1016/j.bbadis.2016.11.005. View

2.
Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E, Johnson K . Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature. 2018; 556(7702):501-504. PMC: 6037913. DOI: 10.1038/s41586-018-0052-z. View

3.
Medzhitov R, Janeway Jr C . Innate immunity. N Engl J Med. 2000; 343(5):338-44. DOI: 10.1056/NEJM200008033430506. View

4.
Bui D, Ravasz D, Chinopoulos C . The Effect of 2-Ketobutyrate on Mitochondrial Substrate-Level Phosphorylation. Neurochem Res. 2019; 44(10):2301-2306. PMC: 6776489. DOI: 10.1007/s11064-019-02759-8. View

5.
Zhang F, Casey P . Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem. 1996; 65:241-69. DOI: 10.1146/annurev.bi.65.070196.001325. View