Advances in crosstalk among innate immune pathways activated by mitochondrial DNA

Guangwei Tao; Wenyan Liao; Jiafeng Hou; Xinmiao Jiang; Xin Deng; Guodong Chen; Chengming Ding

doi:10.1016/j.heliyon.2024.e24029

Advances in crosstalk among innate immune pathways activated by mitochondrial DNA

Heliyon. 2024 Jan 3;10(1):e24029. doi: 10.1016/j.heliyon.2024.e24029. eCollection 2024 Jan 15.

Authors

Guangwei Tao^{1

2}, Wenyan Liao³, Jiafeng Hou¹, Xinmiao Jiang¹, Xin Deng¹, Guodong Chen¹, Chengming Ding¹

Affiliations

¹ The First Affiliated Hospital, Department of Hepatopancreatobiliary Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
² The First Affiliated Hospital of Anhui Medical University, Clinical Immunology Institute, Anhui Medical University, Hefei, Anhui, 230032, China.
³ The First Affiliated Hospital, Department of Gynaecology and Obstetrics, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.

Abstract

Mitochondria are not only the power plant for intracellular oxidative phosphorylation and ATP synthesis, but also involved in cell proliferation, differentiation, signaling and apoptosis. Recent studies have shown that mitochondria play an important role in other pathophysiological functions in addition to cellular energy metabolism. Mitochondria release mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) to activate Toll-like receptor 9 (TLR9), NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune signaling pathways against foreign pathogenic microorganisms. The innate immune response not only promotes antimicrobial immune defense and regulates antiviral signaling, but their overactivation also induces the onset and progression of inflammatory diseases. In this paper, we review the role of mtDNA in the activation of innate immune signaling pathways and the crosstalk among innate immune signaling pathways activated by mtDNA, providing clues for the study of inflammatory diseases caused by mtDNA cytoplasmic translocation.

Keywords: NLRP3 inflammasome; TLR9; cGAS-STING signaling pathway; mtDNA.

Publication types

Review