Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan, 31151, Republic of Korea.
Exp Mol Med. 2023 Dec;55(12):2508-2518. doi: 10.1038/s12276-023-01121-x. Epub 2023 Dec 1.
Mitochondria participate in a wide range of cellular processes. One essential function of mitochondria is to be a platform for antiviral signaling proteins during the innate immune response to viral infection. Recently, studies have revealed that mitochondrion-derived DNAs and RNAs are recognized as non-self molecules and act as immunogenic ligands. More importantly, the cytosolic release of these mitochondrial nucleic acids (mt-NAs) is closely associated with the pathogenesis of human diseases accompanying aberrant immune activation. The release of mitochondrial DNAs (mtDNAs) via BAX/BAK activation and/or VDAC1 oligomerization activates the innate immune response and inflammasome assembly. In addition, mitochondrial double-stranded RNAs (mt-dsRNAs) are sensed by pattern recognition receptors in the cytosol to induce type I interferon expression and initiate apoptotic programs. Notably, these cytosolic mt-NAs also mediate adipocyte differentiation and contribute to mitogenesis and mitochondrial thermogenesis. In this review, we summarize recent studies of innate immune signaling pathways regulated by mt-NAs, human diseases associated with mt-NAs, and the emerging physiological roles of mt-NAs.
线粒体参与广泛的细胞过程。线粒体的一个基本功能是在病毒感染的先天免疫反应中充当抗病毒信号蛋白的平台。最近的研究表明，线粒体衍生的 DNA 和 RNA 被识别为非自身分子，并作为免疫原性配体发挥作用。更重要的是，这些线粒体核酸（mt-NAs）的细胞质释放与伴随异常免疫激活的人类疾病的发病机制密切相关。通过 BAX/BAK 激活和/或 VDAC1 寡聚化释放线粒体 DNA（mtDNA）激活先天免疫反应和炎性小体组装。此外，线粒体双链 RNA（mt-dsRNAs）被细胞质中的模式识别受体识别，以诱导 I 型干扰素表达并启动凋亡程序。值得注意的是，这些细胞质 mt-NAs 还介导脂肪细胞分化，并有助于有丝分裂和线粒体产热。在这篇综述中，我们总结了 mt-NAs 调节的先天免疫信号通路、与 mt-NAs 相关的人类疾病以及 mt-NAs 的新兴生理作用的最新研究进展。
