Mitochondrial DNA release and sensing in innate immune responses

作者：Jordyn J. VanPortfliet, Cole Chute, Yuanjiu Lei, Timothy E. Shutt, A. Phillip West · 发表于：Human Molecular Genetics · 年份：2024 · DOI：10.1093/hmg/ddae031 · 被引用次数：53 · 研究领域：interferon and immune responses、Immune Response and Inflammation、Inflammasome and immune disorders

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.