COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.
COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.
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COX7AR 是一种应激诱导的线粒体 COX 亚基，可促进乳腺癌恶性肿瘤
DOI：
10.1038/srep31742
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发表时间：
2016-08-23
影响因子：
4.6
通讯作者：
Grossman LI
中科院分区：
文献类型：
--
作者：
Zhang K;Wang G;Zhang X;Hüttemann PP;Qiu Y;Liu J;Mitchell A;Lee I;Zhang C;Lee JS;Pecina P;Wu G;Yang ZQ;Hüttemann M;Grossman LI
细胞色素c氧化酶（Cytochrome c oxidase， COX）是线粒体呼吸链的末端酶，在调节线粒体能量产生和细胞存活中起关键作用。COX亚基VIIa多肽2样蛋白（COX 7ar）是一种新的COX亚基，最近被发现参与线粒体超复合体组装和线粒体呼吸活性。在这里，我们报道了COX7AR在高能量需求组织中表达，如大脑、心脏、肝脏和侵袭性人类乳腺癌细胞。在刺激能量代谢的细胞应激下，COX 7ar被诱导并纳入线粒体COX复合体。在功能上，COX7AR促进人乳腺上皮细胞的细胞能量产生。功能增益和功能丧失分析表明，COX7AR是人类乳腺癌细胞维持较高增殖、克隆形成和侵袭率所必需的。总之，我们的研究表明，COX 7ar是一种应激诱导的线粒体COX亚基，促进了人类乳腺癌的恶性发展。这些发现对于理解和治疗人类乳腺癌以及与线粒体能量代谢相关的疾病具有重要意义。
Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism.