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.

Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy

“…Similarly, fractional increases in mitochondrial fusion or mitochondrial mass have been seen after lower doses of low-LET and high-LET radiation to neurons and lung tumor cells [36, 40]. In an effort to aid repair after irradiation, a cell acquires a greater capacity to produce ATP, offset by mitochondrial dysfunction denoted by more mtROS production [10, 38].…”

Bisperoxovandium (pyridin‐2‐squaramide) targets both PTEN and ERK1/2 to confer neuroprotection

“…The cells were incubated with MTT for 1 h, then lysed with DMSO and left at room temperature in the dark overnight. The lysates were then read on a plate reader (PowerWave X, Bio‐Tek, Winooski, State, USA) at an absorbance wavelength of 540 nm (Qu et al, ; Chien et al, ).…”

Assessment of Nuclear and Mitochondrial DNA, Expression of Mitochondria-Related Genes in Different Brain Regions in Rats after Whole-Body X-ray Irradiation

“…It has been shown earlier in different studies that, depending on radiation dose and the time after radiation exposure, different modulations of mitochondrial genes expression can be seen in various cells and animal tissues (in vivo) [36,37]. Chien et al reported that irradiation of hippocampal neurons at low doses leads to enhanced expression of genes encoding OXPHOS complexes I and III [38]. Apparently, a dramatic decrease in the expression of ND2, CytB and ATP5O genes in the brain regions is responsible for perturbation of OXPHOS with an increase in RONS and may induce mitochondrial dysfunction.…”

“…In contrast to this view, Chien et al wrote that low doses of IR may positively influence the regulation of mitochondrial quality and preservation of mitochondrial functions to provide neuronal viability [38]. Interestingly, there is an abundance of data on the important role of alterations to mitochondrial dynamics in pathogenesis of neurodegenerative diseases and on pathologies found during this process [45].…”