Division of Basic Radiation Bioscience, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea.
Radiological & Medico-Oncological Sciences, University of Science & Technology, Daejeon 34113, Korea.
Cells. 2019 Aug 21;8(9):950. doi: 10.3390/cells8090950.
An understanding of cellular processes that determine the response to ionizing radiation exposure is essential for improving radiotherapy and assessing risks to human health after accidental radiation exposure. Radiation exposure leads to many biological effects, but the mechanisms underlying the metabolic effects of radiation are not well known. Here, we investigated the effects of radiation exposure on the metabolic rate and mitochondrial bioenergetics in skeletal muscle. We show that ionizing radiation increased mitochondrial protein and mass and enhanced proton leak and mitochondrial maximal respiratory capacity, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, mice and cells treated with radiation became energetically efficient and displayed increased fatty acid and amino acid oxidation metabolism through the citric acid cycle. Finally, we demonstrate that radiation-induced alterations in mitochondrial energy metabolism involved adenosine monophosphate-activated kinase signaling in skeletal muscle. Together, these results demonstrate that alterations in mitochondrial mass and function are important adaptive responses of skeletal muscle to radiation.
了解决定对电离辐射暴露反应的细胞过程对于改善放射治疗和评估意外辐射暴露后对人类健康的风险至关重要。辐射暴露会导致许多生物学效应，但辐射代谢效应的机制尚不清楚。在这里，我们研究了辐射暴露对骨骼肌代谢率和线粒体生物能学的影响。我们表明，电离辐射增加了线粒体蛋白和质量，并增强了质子泄漏和线粒体最大呼吸能力，导致用于解偶联反应的线粒体呼吸部分增加。因此，接受辐射的小鼠和细胞变得具有能量效率，并通过柠檬酸循环显示出增加的脂肪酸和氨基酸氧化代谢。最后，我们证明辐射诱导的线粒体能量代谢改变涉及骨骼肌中的单磷酸腺苷激活的蛋白激酶信号。总之，这些结果表明，线粒体质量和功能的改变是骨骼肌对辐射的重要适应性反应。
