Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression
Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression
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DOI：
10.1038/onc.2010.193
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发表时间：
2010-07-01
期刊：
影响因子：
8
通讯作者：
Luthra, R.
中科院分区：
文献类型：
--
作者：
Chen, Z.;Li, Y.;Luthra, R.
在包括缺氧在内的各种病理条件下线粒体功能受损的机制仍然很大程度上未知。最近的研究表明，microRNA-210（miR-210）在缺氧诱导因子1α的调控下由缺氧诱导，对缺氧微环境下的细胞生存具有重要作用。因此，我们假设miR-210在调节线粒体代谢中发挥作用，并研究了正常和缺氧条件下miR-210对癌细胞系线粒体功能的影响。我们的结果表明，miR-210 降低线粒体功能并上调糖酵解，从而使癌细胞对糖酵解抑制剂更加敏感。 miR-210 还可以激活活性氧 (ROS) 的产生。 ISCU（铁硫簇支架同源物）和COX10（细胞色素c氧化酶组装蛋白）是线粒体电子传递链和三羧酸循环的两个重要因子，已被确定为miR-210的潜在靶标。 miR-210 调节线粒体功能的独特方式揭示了微环境应激、氧化磷酸化、ROS 和铁稳态之间的 miRNA 介导的联系。癌基因 (2010) 29, 4362-4368; doi：10.1038/onc.2010.193； 2010 年 5 月 24 日在线发布
The mechanisms of compromised mitochondrial function under various pathological conditions, including hypoxia, remain largely unknown. Recent studies have shown that microRNA-210 (miR-210) is induced by hypoxia under the regulation of hypoxia-inducible factor-1 alpha and has an important role in cell survival under hypoxic microenvironment. Hence, we hypothesized that miR-210 has a role in regulating mitochondrial metabolism and investigated miR-210 effects on mitochondrial function in cancer cell lines under normal and hypoxic conditions. Our results demonstrate that miR-210 decreases mitochondrial function and upregulates the glycolysis, thus make cancer cells more sensitive to glycolysis inhibitor. miR-210 can also activate the generation of reactive oxygen species (ROS). ISCU (iron-sulfur cluster scaffold homolog) and COX10 (cytochrome c oxidase assembly protein), two important factors of the mitochondria electron transport chain and the tricarboxylic acid cycle have been identified as potential targets of miR-210. The unique means by which miR-210 regulates mitochondrial function reveals an miRNA-mediated link between microenvironmental stress, oxidative phosphorylation, ROS and iron homeostasis. Oncogene (2010) 29, 4362-4368; doi:10.1038/onc.2010.193; published online 24 May 2010