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

Zhang, Wen; Chen, Shi; Guan, Hua; Zhou, Pingkun

doi:10.1016/j.radmp.2022.05.002

Cited by 3 publications

(4 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some damage stresses, such as H 2 O 2 , high glucose, LPS, and IR, were reported to increase mtDNA release into the cytosol [ 41 , 42 , 43 , 44 , 45 , 46 ]. One critical role of cytosolic mtDNA is to activate cGAS signal transduction and downstream inflammatory and immune responses [ 21 ]. Here, we confirmed that the increased cytosolic mtDNA plays a critical role in determining the sensitivity of cells to IR damage through activating the cGAS signal pathway ( Figure 8 ).…”

Section: Discussionmentioning

confidence: 99%

“…When these rescue measures fail, mitochondria release mtDNA, which triggers an innate immune response [ 19 ]. The mitochondrial DNA is released into the cytoplasm, where it is recognized and activated by the cyclic GMP-AMP synthase (cGAS) [ 20 , 21 ]. More and more reports have confirmed that the activation of the cGAS-STING pathway shows great potential as an innate immunosensor in tumor cells and immune cells.…”

Section: Introductionmentioning

confidence: 99%

“…Delivering corresponding agonists through appropriate drug delivery systems to enhance the immune system‘s ability to fight cancer can greatly promote the efficacy of cancer biotherapy [ 22 , 23 ]. In addition, the cytosolic DNA-cGAS/STING pathway can also treat cancer through radiation-induced non-targeted effects [ 21 ]. As a pattern recognition receptor (PRR), cGAS can detect various pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and finally produce I-IFN [ 20 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice

Guan

Zhang

Xie

et al. 2023

IJMS

View full text Add to dashboard Cite

Mitochondrion is an important organelle of eukaryotic cells and a critical target of ionizing radiation (IR) outside the nucleus. The biological significance and mechanism of the non-target effect originating from mitochondria have received much attention in the field of radiation biology and protection. In this study, we investigated the effect, role, and radioprotective significance of cytosolic mitochondrial DNA (mtDNA) and its associated cGAS signaling on hematopoietic injury induced by IR in vitro culture cells and in vivo total body irradiated mice in this study. The results demonstrated that γ-ray exposure increases the release of mtDNA into the cytosol to activate cGAS signaling pathway, and the voltage-dependent anion channel (VDAC) may contribute to IR-induced mtDNA release. VDAC1 inhibitor DIDS and cGAS synthetase inhibitor can alleviate bone marrow injury and ameliorate hematopoietic suppression induced by IR via protecting hematopoietic stem cells and adjusting subtype distribution of bone marrow cells, such as attenuating the increase of the F4/80+ macrophage proportion in bone marrow cells. The present study provides a new mechanistic explanation for the radiation non-target effect and an alternative technical strategy for the prevention and treatment of hematopoietic acute radiation syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice

Guan

Zhang

Xie

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Moreover, radiation-induced mtROS modulates the inflammatory response by affecting the mRNA expression of TNF-α, IL-6, and IL-12p40 in BMDM [ 272 ]. Mitochondrial stress activates the cGAS and AIM2 signalling pathways, subsequently initiating inflammatory responses through radiation-induced non-target effects [ 273 ]. SIRT3 is involved in persistent radiation-induced damage to the liver.…”

Section: Ionizing Radiation and Saspmentioning

confidence: 99%

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Ibragimova,

Kussainova,

Aripova

et al. 2024

Cells

View full text Add to dashboard Cite

This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure.

show abstract

Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1

Guo,

Han,

Yao

et al. 2024

Journal of Biological Chemistry

View full text Add to dashboard Cite

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

Cited by 3 publications

References 131 publications

Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice

Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1

Contact Info

Product

Resources

About