Oncotarget

Research Papers: Pathology:

Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons

Ling Chien, Wun-Ke Chen, Szu-Ting Liu, Chuang-Rung Chang, Mou-Chieh Kao, Kuan-Wei Chen, Shih-Che Chiu, Ming-Ling Hsu, I-Chou Hsiang, Yu-Jen Chen and Linyi Chen _

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Oncotarget. 2015; 6:30628-30639. https://doi.org/10.18632/oncotarget.5790

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Abstract

Ling Chien1,*, Wun-Ke Chen4,*, Szu-Ting Liu1,*, Chuang-Rung Chang2,3, Mou-Chieh Kao1, Kuan-Wei Chen1, Shih-Che Chiu4, Ming-Ling Hsu4, I-Chou Hsiang4, Yu-Jen Chen4 and Linyi Chen1,2,3

1 Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.

2 Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.

3 Center for Brain Research, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.

4 Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan, R.O.C.

* These authors have contributed equally to this work

Correspondence to:

Linyi Chen, email:

Yu-Jen Chen, email:

Keywords: radiation therapy, hippocampal neurons, mitochondrial fusion, low dose radiation, Pathology Section

Received: May 25, 2015 Accepted: September 07, 2015Published: September 22, 2015

Abstract

High energy ionizing radiation can cause DNA damage and cell death. During clinical radiation therapy, the radiation dose could range from 15 to 60 Gy depending on targets. While 2 Gy radiation has been shown to cause cancer cell death, studies also suggest a protective potential by low dose radiation. In this study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal neurons are post-mitotic, this result reveals a possibility that 0.2 Gy irradiation may increase mitochondrial activity to cope with stimuli. Maintaining neural plasticity is an energy-demanding process that requires high efficient mitochondrial function. We thus hypothesized that low dose radiation may regulate mitochondrial dynamics and function to ensure survival of neurons. Our results showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy irradiation promoted the mitochondria fusion, resulting in part from the increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1 fission protein trafficking to the mitochondria. Accompanying with the increased mitochondrial fusion, the expressions of complexes I and III of the electron transport chain were also increased. These findings suggest that, hippocampal neurons undergo increased mitochondrial fusion to modulate cellular activity as an adaptive mechanism in response to low dose radiation.


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