Mitochondrial ACOD1/IRG1 in infection and sterile inflammation

Runliu Wu; Rui Kang; Daolin Tang

doi:10.1016/j.jointm.2022.01.001

Mitochondrial ACOD1/IRG1 in infection and sterile inflammation

J Intensive Med. 2022 Feb 12;2(2):78-88. doi: 10.1016/j.jointm.2022.01.001. eCollection 2022 Apr.

Authors

Runliu Wu¹, Rui Kang², Daolin Tang²

Affiliations

¹ Department of Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
² Department of Surgery, UT Southwestern Medical Center, Dallas, Texas 75390, USA.

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.

Keywords: Aconitate decarboxylase 1 (ACOD1); Disease; Inflammation; Metabolism; Sepsis.

Publication types

Review