The Jackson Laboratory, Bar Harbor, ME 04609, United States.
Department of Microbial Pathogenesis and Immunology, School of Medicine, Texas A&M University, Bryan, TX 77807, United States.
Hum Mol Genet. 2024 May 22;33(R1):R80-R91. doi: 10.1093/hmg/ddae031.
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.
线粒体是多功能细胞器，是包括代谢、信号转导和程序性细胞死亡在内的一系列细胞途径的核心。线粒体也是哺乳动物免疫反应的关键驱动因素，作为先天免疫信号的支架，调节免疫细胞激活所需的代谢开关，并释放促进炎症的激动剂。线粒体 DNA（mtDNA）是一种有效的免疫刺激激动剂，可在多种哺乳动物细胞类型中引发促炎和 I 型干扰素反应。在这里，我们回顾了最近在细胞质和细胞外空间释放后，先天免疫系统的核酸传感器检测 mtDNA 的进展。我们还讨论了 mtDNA 释放和感应的相互作用如何影响与健康和疾病相关的细胞先天免疫终点。
