Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways
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 w...
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| Format: | Article |
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Elsevier
2022-06-01
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| Series: | Radiation Medicine and Protection |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666555722000260 |
| _version_ | 1797712138189406208 |
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| author | Wen Zhang Shi Chen Hua Guan Ping-Kun Zhou |
| author_facet | Wen Zhang Shi Chen Hua Guan Ping-Kun Zhou |
| author_sort | Wen Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T07:17:21Z |
| format | Article |
| id | doaj.art-9268648c103743f89afa7441d83450b3 |
| institution | Directory Open Access Journal |
| issn | 2666-5557 |
| language | English |
| last_indexed | 2024-03-12T07:17:21Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
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| series | Radiation Medicine and Protection |
| spelling | doaj.art-9268648c103743f89afa7441d83450b32023-09-02T22:43:58ZengElsevierRadiation Medicine and Protection2666-55572022-06-01324755Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathwaysWen Zhang0Shi Chen1Hua Guan2Ping-Kun Zhou3Hengyang Medical School, University of South China, Hengyang, Hunan Province 421001, China; Beijing Key Laboratory for Radiobiology, Department of Radiation Biology, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaHengyang Medical School, University of South China, Hengyang, Hunan Province 421001, China; Beijing Key Laboratory for Radiobiology, Department of Radiation Biology, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaBeijing Key Laboratory for Radiobiology, Department of Radiation Biology, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaHengyang Medical School, University of South China, Hengyang, Hunan Province 421001, China; Beijing Key Laboratory for Radiobiology, Department of Radiation Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China; Corresponding author. Hengyang Medical School, University of South China, Hengyang, Hunan Province, 421001, China.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.http://www.sciencedirect.com/science/article/pii/S2666555722000260Non-targeted effectMitochondrial DNAcGASIonizing radiationImmune responseRadiotherapy |
| spellingShingle | Wen Zhang Shi Chen Hua Guan Ping-Kun Zhou Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways Radiation Medicine and Protection Non-targeted effect Mitochondrial DNA cGAS Ionizing radiation Immune response Radiotherapy |
| title | Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways |
| title_full | Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways |
| title_fullStr | Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways |
| title_full_unstemmed | Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways |
| title_short | Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways |
| title_sort | radiation induced non targeted effect of immunity provoked by mitochondrial dna damage triggered cgas aim2 pathways |
| topic | Non-targeted effect Mitochondrial DNA cGAS Ionizing radiation Immune response Radiotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2666555722000260 |
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