Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 730000, China.
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 730000, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Biochem Biophys Res Commun. 2018 Jun 12;500(4):958-965. doi: 10.1016/j.bbrc.2018.04.214. Epub 2018 May 2.
Although mitochondria are known to play an important role in radiation-induced cellular damage, the mechanisms by which ionizing radiation modulates mitochondrial dynamics are largely unknown. In this study, human cervical carcinoma cell line HeLa was used to demonstrate the different modes of mitochondrial network in response to different quality radiations such as low linear energy transfer (LET) X-rays and high-LET carbon ions. Mitochondria fragmented into punctate and clustered ones upon carbon ion irradiation in a dose- and LET-dependent manner, which was associated with apoptotic cell death. In contrast, low-dose X-ray irradiation promoted mitochondrial fusion while mitochondrial fission was detected until the radiation dose was more than 1 Gy. This fission was driven by ERK1/2-mediated phosphorylation of Drp1 on Serine 616. Inhibition of mitochondrial fragmentation suppressed the radiation-induced apoptosis and thus enhanced the resistance of cells to carbon ions and high-dose X-rays, but not for cells irradiated with X-rays at the low dose. Our results suggest that radiations of different qualities cause diverse changes of mitochondrial dynamics in cancer cells, which play an important role in determining the cell fate.
虽然线粒体在辐射诱导的细胞损伤中起着重要作用，但电离辐射调节线粒体动力学的机制在很大程度上尚不清楚。在这项研究中，用人宫颈癌细胞系 HeLa 证明了线粒体网络在不同质量辐射（如低线性能量传递（LET）X 射线和高 LET 碳离子）下的不同模式。线粒体在碳离子照射下呈点状和簇状碎片化，呈剂量和 LET 依赖性，与细胞凋亡有关。相比之下，低剂量 X 射线照射促进线粒体融合，而在线粒体分裂直到辐射剂量超过 1Gy 时才被检测到。这种分裂是由 ERK1/2 介导的 Drp1 丝氨酸 616 磷酸化驱动的。抑制线粒体碎片化可抑制辐射诱导的细胞凋亡，从而增强细胞对碳离子和高剂量 X 射线的抗性，但对低剂量 X 射线照射的细胞没有影响。我们的结果表明，不同质量的辐射会导致癌细胞中线粒体动力学的不同变化，这对于确定细胞命运起着重要作用。
