title: Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons.
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.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Ling
authors.initials: L
authors.lastname: Chien
authors.affiliation: Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Wun-Ke
authors.initials: WK
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Szu-Ting
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.|Center for Brain Research, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Chuang-Rung
authors.initials: CR
authors.lastname: Chang
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Mou-Chieh
authors.initials: MC
authors.lastname: Kao
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Shih-Che
authors.initials: SC
authors.lastname: Chiu
authors.affiliation: Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Hsu
authors.affiliation: Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: I-Chou
authors.initials: IC
authors.lastname: Hsiang
authors.affiliation: Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.|Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.|Center for Brain Research, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000066670:Cell Plasticity / Q000502:physiology; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics; D034281:Dynamins / Q000378:metabolism; D042967:Electron Transport Complex I / Q000096:biosynthesis*; D014450:Electron Transport Complex III / Q000096:biosynthesis*; D020558:GTP Phosphohydrolases; D018628:Gene Dosage / Q000235:genetics; D006624:Hippocampus / Q000528:radiation effects*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology / Q000528:radiation effects; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000528:radiation effects*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009474:Neurons / Q000528:radiation effects*; D010084:Oxidation-Reduction / Q000528:radiation effects; D021381:Protein Transport / Q000528:radiation effects; D011839:Radiation, Ionizing; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; C519851:Dnm1l protein, rat; D034281:Dynamins; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III
keywords: Pathology Section; hippocampal neurons; low dose radiation; mitochondrial fusion; radiation therapy