Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways
Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways
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线粒体 DNA 损伤引发的辐射诱导的非靶向免疫效应触发了 cGAS/AIM2 通路
DOI：
10.1016/j.radmp.2022.05.002
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发表时间：
2022-05
影响因子：
--
通讯作者：
Zhou PK
中科院分区：
文献类型：
--
作者：
Zhang W;Chen S;Guan H;Zhou PK
非靶向效应是对以核基因组DNA为核心靶点的辐射生物学经典靶点理论的重要补充。辐射靶理论的原理是假设一个生物体或细胞有一个或多个敏感点或目标，直接被辐射击中或失去活性会导致相当大的损伤和死亡事件。最近的研究结果表明，不仅细胞核，细胞的其他部分也可以被认为是可能的靶点。线粒体被认为是启动非靶向效应的关键细胞器。近年来的一系列研究提供了大量的证据和可靠的数据，深刻地促进了对辐照细胞中线粒体发出的辐射诱导的非靶向效应的理解，如主要的表观性能、信号通路和生物学意义。线粒体基因组比核基因组对基因毒性更敏感。电离辐射可通过增加线粒体ROS直接或间接诱导mtdna双链断裂。在应激条件下，线粒体DNA （mtDNA）片段被释放到细胞质中。胞浆mtdna被cGAS和AIM2蛋白感知并激活相应的信号通路，产生相关的炎症和免疫反应。这些新开发的线粒体dna启动途径可能会促进靶向治疗的发展，以防止正常组织毒性以及放射免疫治疗，这是癌症治疗的新兴趋势。本文主要从辐射的非靶向效应方面探讨mtdna触发免疫应答的cGAS/AIM2信号通路的机制及生物学意义。
Non-targeted effect is an important complement to the classical target theory of radiation biology which takes nuclear genomic DNA as the core target. The principle of radiation target theory is to assume that an organism or cell has one or more sensitive points or targets, hit and inactivation of which directly by radiation leads to considerable damage and the death event. Recent findings indicate that not only cell nucleus but also other cellular parts can be considered as possible targets. Mitochondrion is considered as a critical organelle where the non-targeted effect is initiated. A series of recent studies have provided substantial evidence and solid data which profoundly facilitate the understanding of radiation-induced non-targeted effects emitted from mitochondrion in the irradiated cells, such the major apparent performances, signaling pathways and biological significance. Mitochondrial genome is more sensitive to genotoxic than nuclear genome. Ionizing radiation can induce mtDNAs double-strand breaks directly or indirectly via increased mitochondrial ROS. Under stress conditions, mitochondrial DNA (mtDNA) fragments are released into the cytoplasm. The cytosol mtDNAs are sensed by cGAS and AIM2 proteins and they activate the corresponding signaling pathways, generating relevant inflammatory and immune responses. These newly developed mitochondrial DNA-initiating pathways may boost the development of targeted therapies for preventing normal tissue toxicity as well as radio-immunotherapy, an emerging trend for cancer therapies. Here we focus and discuss the mechanisms and biological significance of mtDNA-triggering cGAS/AIM2 signaling pathways of immune response from the aspect of non-targeted effect of radiation.
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影响因子：
13.5
作者：
Ma, Hui;Kang, Zhihua;Xia, Bing
通讯作者：
Xia, Bing
DOI：
10.1126/science.aaf7532
发表时间：
2016-11-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hu B;Jin C;Li HB;Tong J;Ouyang X;Cetinbas NM;Zhu S;Strowig T;Lam FC;Zhao C;Henao-Mejia J;Yilmaz O;Fitzgerald KA;Eisenbarth SC;Elinav E;Flavell RA
通讯作者：
Flavell RA
影响因子：
8.8
作者：
Chen, S.;Zhao, Y.;Han, W.;Zhao, G.;Zhu, L.;Wang, J.;Bao, L.;Jiang, E.;Xu, A.;Hei, T. K.;Yu, Z.;Wu, L.
通讯作者：
Wu, L.
DOI：
10.1084/jem.20171749
发表时间：
2017-12-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Swanson KV;Junkins RD;Kurkjian CJ;Holley-Guthrie E;Pendse AA;El Morabiti R;Petrucelli A;Barber GN;Benedict CA;Ting JP
通讯作者：
Ting JP
影响因子：
64.8
作者：
Oka, Takafumi;Hikoso, Shungo;Yamaguchi, Osamu;Taneike, Manabu;Takeda, Toshihiro;Tamai, Takahito;Oyabu, Jota;Murakawa, Tomokazu;Nakayama, Hiroyuki;Nishida, Kazuhiko;Akira, Shizuo;Yamamoto, Akitsugu;Komuro, Issei;Otsu, Kinya
通讯作者：
Otsu, Kinya