Allotopic expression of a mitochondrial alternative oxidase confers cyanide resistance to human cell respiration
Allotopic expression of a mitochondrial alternative oxidase confers cyanide resistance to human cell respiration
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DOI：
10.1038/sj.embor.7400601
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发表时间：
2006-03-01
期刊：
影响因子：
7.7
通讯作者：
Rustin, P
中科院分区：
文献类型：
--
作者：
Hakkaart, GAJ;Dassa, EP;Rustin, P
人类线粒体呼吸与大多数植物，微生物甚至一些后生动物的呼吸不同，因为它仅通过高度氰化物敏感的酶细胞色素c氧化酶来减少分子氧。在这里，我们表明，表达的氰化物不敏感的替代氧化酶（AOX），最近确定的海鞘玻璃海鞘，是很好的耐受培养的人类细胞，并赋予壮观的抗氰化物线粒体底物氧化。表达的AOX似乎仅限于线粒体。AOX参与电子流是由呼吸链（RC）的高度还原的氧化还原状态触发的，并由丙酮酸盐增强;否则，酶基本上保持无活性。AOX表达有望成为限制人类细胞和整个动物中RC缺陷的有害后果的有价值的工具。
Human mitochondrial respiration is distinct from that of most plants, microorganisms and even some metazoans in that it reduces molecular oxygen only through the highly cyanide-sensitive enzyme cytochrome c oxidase. Here we show that expression of the cyanide-insensitive alternative oxidase (AOX), recently identified in the ascidian Ciona intestinalis, is well tolerated by cultured human cells and confers spectacular cyanide resistance to mitochondrial substrate oxidation. The expressed AOX seems to be confined to mitochondria. AOX involvement in electron flow is triggered by a highly reduced redox status of the respiratory chain (RC) and enhanced by pyruvate; otherwise, the enzyme remains essentially inactive. AOX expression promises to be a valuable tool to limit the deleterious consequences of RC deficiency in human cells and whole animals.