The Role of Mitochondria in the Radiation-Induced Bystander Effect in Human Lymphoblastoid Cells

Rajendran, Sountharia; Harrison, Scott H.; Thomas, Robert A.; Tucker, James D.

doi:10.1667/rr2296.1

Cited by 33 publications

(25 citation statements)

References 58 publications

(56 reference statements)

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“…Several endpoints have been tested to examine mitochondrial dysfunction in irradiated cells and their progeny. For example, early and late generation of radiation-induced mitochondrial ROS/RNS mediates changes in mitochondrial DNA copy number [141], mutations [142] and gene expression [143; 144], autophagy [145; 146], apoptosis [147; 148; 149], propagation of non-targeted responses [73; 150; 151; 152; 153; 154; 155], the induction of nuclear DNA damage [156], genomic instability [157], neoplastic transformation [158], and degenerative conditions [37; 63; 159] among other outcomes [2; 37]. We investigated effects of ionizing radiation on mitochondrial protein import, assembly of large protein complexes, protein oxidation and activity of metabolic and antioxidant enzymes [10; 11; 45; 48; 160; 161].…”

Section: Mitochondria and Delayed Effects Of Ionizing Radiationmentioning

confidence: 99%

Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

2012

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Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes.

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Section: Mitochondria and Delayed Effects Of Ionizing Radiationmentioning

confidence: 99%

Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

2012

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“…Mitochondria, the location of the COX2 gene ( MT-COX2 ), are potent generators of free radicals such as NO, and have been shown to be important in non-targeted effects. This was shown when reduced bystander effect was observed in cells deficient in mitochondria [67], or in cells having critical mutations in mitochondrial DNA [68]. …”

Section: Potential Mechanisms In the Mediation Of Non-targeted Effmentioning

confidence: 99%

Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects

et al. 2015

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A spectrum of radiation-induced non-targeted effects has been reported during the last two decades since Nagasawa and Little first described a phenomenon in cultured cells that was later called the “bystander effect”. These non-targeted effects include radiotherapy-related abscopal effects, where changes in organs or tissues occur distant from the irradiated region. The spectrum of non-targeted effects continue to broaden over time and now embrace many types of exogenous and endogenous stressors that induce a systemic genotoxic response including a widely studied tumor microenvironment. Here we discuss processes and factors leading to DNA damage induction in non-targeted cells and tissues and highlight similarities in the regulation of systemic effects caused by different stressors.

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“…We previously reported that IR affects various aspects of mitochondrial physiology, including mitochondrial respiration, ATP production, and mitochondrial dynamics [12, 13]. In addition, mitochondria are also suggested to be involved in radiation-induced intra- and intercellular signaling [14–16]. These findings indicate that mitochondria are likely to be an important target of IR and may play a critical role in cellular radioresponses.…”

Section: Introductionmentioning

confidence: 98%

Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts

Yamamori

Sasagawa

Ichii

et al. 2016

Journal of Radiation Research

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Mitochondria strongly contribute to the maintenance of cellular integrity through various mechanisms, including oxidative adenosine triphosphate production and calcium homeostasis regulation. Therefore, proper regulation of the abundance, distribution and activity of mitochondria is crucial for the maintenance of cellular homeostasis. Previous studies have shown that ionizing radiation (IR) alters mitochondrial functions, suggesting that mitochondria are likely to be an important target of IR. Though IR reportedly influences cellular mitochondrial abundance, the mechanism remains largely unknown. In this study, we examined how IR influences mitochondrial abundance in mouse fibroblasts. When mouse NIH/3T3 cells were exposed to X-rays, a time-dependent increase was observed in mitochondrial DNA (mtDNA) and mitochondrial mass, indicating radiation-induced upregulation of mitochondrial abundance. Meanwhile, not only did we not observe a significant change in autophagic activity after irradiation, but in addition, IR hardly influenced the expression of two mitochondrial proteins, cytochrome c oxidase subunit IV and cytochrome c, or the mRNA expression of Polg, a component of DNA polymerase γ. We also observed that the expression of transcription factors involved in mitochondrial biogenesis was only marginally affected by IR. These data imply that radiation-induced upregulation of mitochondrial abundance is an event independent of macroautophagy and mitochondrial biogenesis. Furthermore, we found evidence that IR induced long-term cell cycle arrest and cellular senescence, indicating that these events are involved in regulating mitochondrial abundance. Considering the growing significance of mitochondria in cellular radioresponses, we believe the present study provides novel insights into understanding the effects of IR on mitochondria.

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The Role of Mitochondria in the Radiation-Induced Bystander Effect in Human Lymphoblastoid Cells

Cited by 33 publications

References 58 publications

Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects

Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts

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