Mitochondrial DNA release and sensing in innate immune responses.
Document Type
Article
Publication Date
5-22-2024
Original Citation
VanPortfliet J,
Chute C,
Lei Y,
Shutt T,
West A.
Mitochondrial DNA release and sensing in innate immune responses. Hum Mol Genet. 2024;33(R1):R80-r91
Keywords
JMG, Immunity, Innate, Humans, DNA, Mitochondrial, Mitochondria, Animals, Signal Transduction, Interferon Type I, Inflammation
JAX Source
Hum Mol Genet. 2024;33(R1):R80-r91
ISSN
1460-2083
PMID
38779772
DOI
https://doi.org/10.1093/hmg/ddae031
Grant
This work was supported by award W81XWH-20-1-0150 from the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Programs (A.P.W.), NIH grant R01HL148153 (A.P.W
Abstract
Mitochondria are pleiotropic organelles central to an array of cellular pathways including metabolism, signal transduction, and programmed cell death. Mitochondria are also key drivers of mammalian immune responses, functioning as scaffolds for innate immune signaling, governing metabolic switches required for immune cell activation, and releasing agonists that promote inflammation. Mitochondrial DNA (mtDNA) is a potent immunostimulatory agonist, triggering pro-inflammatory and type I interferon responses in a host of mammalian cell types. Here we review recent advances in how mtDNA is detected by nucleic acid sensors of the innate immune system upon release into the cytoplasm and extracellular space. We also discuss how the interplay between mtDNA release and sensing impacts cellular innate immune endpoints relevant to health and disease.