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Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways

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Radiation Medicine and Protection 2022年第2期3卷 47-55页

作者： Wen Zhang Shi Chen Hua Guan Ping-Kun Zhou Hengyang Medical School University of South ChinaHengyangHunan Province 421001China Beijing Key Laboratory for Radiobiology Department of Radiation BiologyBeijing Institute of Radiation MedicineBeijing 100850China

non-targeted effect is an important complement to the classical target theory of radiation biology which takesnuclear genomic DNA as the core target. The principle of radiation target theory is to assume that an organism orcell has one or more sensitive points or targets, hit and inactivation of which directly by radiation leads toconsiderable damage and the death event. Recent findings indicate that not only cell nucleus but also othercellular parts can be considered as possible targets. Mitochondrion is considered as a critical organelle where thenon-targeted effect is initiated. A series of recent studies have provided substantial evidence and solid data whichprofoundly facilitate the understanding of radiation-induced non-targeted effects emitted from mitochondrion inthe irradiated cells, such the major apparent performances, signaling pathways and biological *** genome is more sensitive to genotoxic than nuclear genome. Ionizing radiation can induce mtDNAsdouble-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 andAIM2 proteins and they activate the corresponding signaling pathways, generating relevant inflammatory andimmune responses. These newly developed mitochondrial DNA-initiating pathways may boost the development oftargeted therapies for preventing normal tissue toxicity as well as radio-immunotherapy, an emerging trend forcancer therapies. Here we focus and discuss the mechanisms and biological significance of mtDNA-triggeringcGAS/AIM2 signaling pathways of immune response from the aspect of non-targeted effect of radiation.

关键词： non-targeted effect Mitochondrial DNA cGAS Ionizing radiation Immune response Radiotherapy

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