Mitochondrial reactive oxygen species and heme, non-heme iron metabolism
Mitochondrial reactive oxygen species and heme, non-heme iron metabolism
复制标题
DOI：
10.1016/j.abb.2020.108695
复制
发表时间：
2021-01-28
影响因子：
3.9
通讯作者：
Matsui, Hirofumi
中科院分区：
文献类型：
--
作者：
Ito, Hiromu;Kurokawa, Hiromi;Matsui, Hirofumi
线粒体是包括人类在内的真核生物产生能量的最重要的细胞器之一。在能量产生过程中，线粒体不断产生活性氧，这是电子传递链中泄漏的电子与氧反应的副产品。反过来，活性氧在介导多种信号传导中起着关键作用，包括那些与神经退行性疾病、心血管疾病和致癌等疾病的发生有关的信号传导。这种来自线粒体活性氧的信号也通过调节转运蛋白的表达来影响细胞内铁的稳态。血红素铁通过HCP1进入细胞，非血红素铁在吸收细胞中通过DMT1转运。细胞内的铁通过运铁蛋白输出并与转铁蛋白结合。在包括红细胞在内的大多数类型的细胞中，转铁蛋白结合铁通过转铁蛋白-转铁蛋白受体系统被结合。我们之前报道了HCP1和DMT1在癌细胞中的表达上调，而锰超氧化物歧化酶（一种线粒体特异性超氧化物歧化酶）的过表达下调了其表达。这些发现表明线粒体活性氧与铁相关的氧化反应有关。最近，线粒体特异性铁转运蛋白mitoferrin被发现，线粒体、铁转运和疾病之间的关系越来越清楚。
Mitochondria are one of the most important organelles for eukaryotes, including humans, to produce energy. In the energy-producing process, mitochondria constantly generate reactive oxygen species as a by-product of electrons leaking out from the electron transport chain react with oxygen. The active oxygen, in turn, plays pivotal roles in mediating several signalings, including those that are implicated in the development of some diseases such as neurodegenerative disease, cardiovascular disease, and carcinogenesis. This signaling, derived from mitochondrial reactive oxygen species, also affects intracellular iron homeostasis by regulating the expression of transporters. Heme iron is incorporated into cells through HCP1, and non-heme iron is transported by DMT1 in absorptive cells. Intracellular iron is exported by ferroportin and bound with transferrin. In most types of cell including erythrocyte, transferrin-bound iron is incorporated through transferrin-transferrin receptor system. We previously reported that the expression of HCP1 and DMT1 was upregulated in cancer cells and that overexpression of manganese superoxide dismutase, which is a mitochondrial-specific superoxide dismutase, downregulated the expression. These findings indicate that mitochondrial reactive oxygen species is associated with iron-related oxidative reactions. Recently, a mitochondria-specific iron transporter, mitoferrin, was identified, and the relationships among mitochondria, iron transportation, and diseases have been increasingly clarified.