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.

铁是人脑中最丰富的金属，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 产生、胚胎神经元发育、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，必须通过平衡铁的吸收、运输和储存来严格调节铁稳态。内体和溶酶体（内溶酶体）是已知含有易于释放的各种阳离子（包括铁和其他金属）的酸性细胞器。^{亚铁 (Fe 2+} )水平的增加会通过芬顿化学反应产生活性氧 (ROS)，这些增加会损害线粒体和基因组 DNA 并促进致癌。大脑中铁的积累与衰老、饮食、疾病和脑出血有关。此外，脑铁代谢失调与癌症发生有关，并可能是世界各地脑肿瘤发病率增加的一个因素。在这里，我们深入了解了 pH 值和溶酶体膜通透性改变内溶酶体中铁积累的机制。此类事件会产生过量的 ROS，导致线粒体 DNA 损伤、裂变和功能障碍，以及细胞核中的 DNA 氧化损伤；所有这些都会促进癌变。更好地了解内溶酶体铁在致癌作用中的作用可能有助于更好地为癌症治疗和预防的战略治疗方案的开发提供信息。