Role of endolysosome function in iron metabolism and brain carcinogenesis.
Role of endolysosome function in iron metabolism and brain carcinogenesis.
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DOI：
10.1016/j.semcancer.2021.06.013
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发表时间：
2021-11
影响因子：
14.5
通讯作者：
Ohm JE
中科院分区：
文献类型：
--
作者：
Halcrow PW;Lynch ML;Geiger JD;Ohm JE
铁是人脑中含量最丰富的金属，是调节多种细胞机制的必需微量元素。铁的一些关键生理作用包括氧化磷酸化和ATP的产生，胚胎神经元的发育，铁-硫簇的形成，以及参与DNA合成和修复的酶的调节。由于铁的生理和病理重要性，必须通过平衡其吸收、运输和储存来严格调节铁的动态平衡。内酶体和溶酶体(内溶酶体)是已知的酸性细胞器，含有容易释放的各种阳离子，包括铁和其他金属。亚铁(Fe2+)含量的增加可通过Fenton化学反应产生活性氧物种(ROS)，这些增加可损伤线粒体和基因组DNA，并促进癌症的发生。大脑中铁的积累与衰老、饮食、疾病和脑出血有关。此外，脑铁代谢的放松与癌症的发生有关，并可能是世界各地脑肿瘤发病率增加的一个促成因素。在这里，我们深入了解了pH和溶酶体膜通透性改变内溶酶体中铁积累的机制。这些事件产生过量的ROS，导致线粒体DNA损伤、分裂和功能障碍，以及细胞核中的DNA氧化损伤；所有这些都促进了癌症的发生。更好地了解内溶酶体铁在癌症发生中的作用，可能有助于更好地为癌症治疗和预防的战略性治疗选择的发展提供信息。
Iron, the most abundant metal in human brain, is an essential microelement that regulates numerous cellular mechanisms. Some key physiological roles of iron include oxidative phosphorylation and ATP production, embryonic neuronal development, formation of iron-sulfur clusters, and the regulation of enzymes involved in DNA synthesis and repair. Because of its physiological and pathological importance, iron homeostasis must be tightly regulated by balancing its uptake, transport, and storage. Endosomes and lysosomes (endolysosomes) are acidic organelles known to contain readily releasable stores of various cations including iron and other metals. Increased levels of ferrous (Fe2+) iron can generate reactive oxygen species (ROS) via Fenton chemistry reactions and these increases can damage mitochondria and genomic DNA as well as promote carcinogenesis. Accumulation of iron in the brain has been linked with aging, diet, disease, and cerebral hemorrhage. Further, deregulation of brain iron metabolism has been implicated in carcinogenesis and may be a contributing factor to the increased incidence of brain tumors around the world. Here, we provide insight into mechanisms by which iron accumulation in endolysosomes is altered by pH and lysosome membrane permeabilization. Such events generate excess ROS resulting in mitochondrial DNA damage, fission, and dysfunction, as well as DNA oxidative damage in the nucleus; all of which promote carcinogenesis. A better understanding of the roles that endolysosome iron plays in carcinogenesis may help better inform the development of strategic therapeutic options for cancer treatment and prevention.
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影响因子：
3.5
作者：
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通讯作者：
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DOI：
10.1124/jpet.112.192138
发表时间：
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影响因子：
3.5
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通讯作者：
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DOI：
10.1046/j.1525-1373.1999.d01-141.x
发表时间：
1999-12-01
影响因子：
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作者：
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通讯作者：
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影响因子：
8
作者：
Basuli D;Tesfay L;Deng Z;Paul B;Yamamoto Y;Ning G;Xian W;McKeon F;Lynch M;Crum CP;Hegde P;Brewer M;Wang X;Miller LD;Dyment N;Torti FM;Torti SV
通讯作者：
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