Oxidized mitochondrial DNA: a protective signal gone awry. Trends Immunol 2023 Mar;44(3):188-200
Date
02/05/2023Pubmed ID
36739208Pubmed Central ID
PMC12045651DOI
10.1016/j.it.2023.01.006Scopus ID
2-s2.0-85148755055 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
Despite the emergence of mitochondria as key regulators of innate immunity, the mechanisms underlying the generation and release of immunostimulatory alarmins by stressed mitochondria remains nebulous. We propose that the major mitochondrial alarmin in myeloid cells is oxidized mitochondrial DNA (Ox-mtDNA). Fragmented Ox-mtDNA enters the cytosol where it activates the NLRP3 inflammasome and generates IL-1β, IL-18, and cGAS-STING to induce type I interferons and interferon-stimulated genes. Inflammasome activation further enables the circulatory release of Ox-mtDNA by opening gasdermin D pores. We summarize new data showing that, in addition to being an autoimmune disease biomarker, Ox-mtDNA converts beneficial transient inflammation into long-lasting immunopathology. We discuss how Ox-mtDNA induces short- and long-term immune activation, and highlight its homeostatic and immunopathogenic functions.
Author List
Xian H, Karin MAuthor
Hongxu Xian PhD Assistant Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
DNA, MitochondrialHumans
Immunity, Innate
Inflammasomes
Mitochondria
Signal Transduction
