中国辐射防护研究院,太原 030006
国家自然科学基金(U216720073)资助项目。
China Institute for Radiation Protection, Taiyuan 030006, China
This work was supported by a grant from The National Natural Science Foundation of China (U216720073).
随着核能在医学、工业等领域的应用,电离辐射损伤时有发生。电离辐射能够诱导蛋白质、DNA等生物大分子损伤,导致细胞凋亡、衰老、癌变等一系列变化。长久以来,细胞核中的DNA通常被认为是电离辐射损伤靶点,其损伤效应备受关注。然而,电离辐射有直接效应和间接效应,间接效应中的活性氧类(ROS)损伤学说认为,电离辐射具有靶点不确定性,除了损伤细胞核DNA外还会损伤细胞器。线粒体作为人体重要细胞器,占据整个细胞容积的30%之多,其中含有的酶与细胞ATP合成、有氧呼吸等生命活动息息相关。值得注意的是,线粒体是除细胞核外人体唯一有DNA存在的细胞器,并且缺乏组蛋白的保护,相比于细胞核更容易受到损伤,因此线粒体是除细胞核以外电离辐射损伤的重要靶点。本文综述了电离辐射对线粒体的损伤效应,从而为辐射防护提供新思路。
In recent years, due to the development of radiotherapy technology and nuclear energy, people have paid more and more attention to the various effects of ionizing radiation on organisms. Ionizing radiation can induce protein, DNA and other biological macromolecules to damage, resulting in apoptosis, senescence, cancer and a series of changes. For a long time, it has been believed that the main target of ionizing radiation damage is DNA in the nucleus. However, it has been reported in recent years that ionizing radiation has both direct and indirect effects, and the theory of ROS damage in the indirect effects believes that ionizing radiation has target uncertainty, so it is not comprehensive enough to evaluate only the DNA damage in the nucleus. It has been reported that ionizing radiation can cause damage to organelles as well as damage to cells. Mitochondria are important damaged organelles because mitochondria occupy as much as 30% of the entire cell volume in the cytoplasm, which contains DNA and related enzymes that are closely related to cellular ATP synthesis, aerobic respiration and other life activities. What is more noteworthy is that mitochondria are the only organelles in which DNA exists in the human body, which makes researchers pay attention to various damage to mitochondrial DNA caused by ionizing radiation (such as double-strand breaks, base mismatching, and fragment loss). Although these damages also occur in the nucleus, mitochondrial DNA is more severely damaged than nuclear DNA due to its lack of histone protection, so mitochondria are important targets of ionizing radiation damage in addition to the nucleus. Mitochondrial DNA is not protected by histones and has little repair ability. When exposed to ionizing radiation, common deletions occur at an increased frequency and are passed on to offspring. For large-scale mitochondrial DNA damage, mitochondria indirectly compensate for the amount of damaged DNA by increasing the number of DNA copies and maintaining the normal function of mitochondrial DNA. Mitochondria are in a state of oxidative stress after exposure to ionizing radiation, and this oxidative stress will promote the change in mitochondrial function. When mitochondria are damaged, the activity of proteins related to aerobic respiration decreases, and oxidative respiration is inhibited to a certain extent. At the same time, a large amount of active superoxide anions are continuously produced to stimulate mitochondrial oxidative stress, and the signal of such damage is transmitted to the surrounding mitochondria, resulting in a cascade of damage reaction, which further activates the signalling pathway between mitochondria and nucleus. The cell nucleus is also in a state of oxidative stress, and finally, the level of free radicals is high, causing secondary damage to the genetic material DNA of mitochondria and nucleus. In this paper, the damage effects of ionizing radiation on mitochondria are reviewed, to provide a new idea for radiation protection.
田连琛,原雅艺,党旭红.线粒体:电离辐射损伤的靶点[J].生物化学与生物物理进展,2025,52(4):836-844
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