Identification and characterization of a human mitochondrial NAD kinase.

Identification and characterization of a human mitochondrial NAD kinase.
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DOI:
10.1038/ncomms2262
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发表时间:
2012
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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NAD激酶是唯一的NADP+生物合成酶。尽管NADP+具有重要意义,但迄今为止尚未在人类线粒体中发现NAD激酶,人类线粒体NADP+的来源仍然难以捉摸。在这里,我们提出的证据表明,功能未知的人类蛋白C5orf33是人类线粒体NAD激酶;这种蛋白质可能代表了人类线粒体NADP+缺失的来源。C5orf33蛋白具有NAD激酶活性,利用ATP或无机多磷酸盐,定位于人HEK293A细胞的线粒体中。在几乎所有组织中,C5orf33 mRNA比人胞浆NAD激酶mRNA更丰富。我们进一步通过数据库检索发现,一些动物和原生生物携带C5orf33同源物作为它们唯一的NADP+生物合成酶,而植物和真菌没有C5orf33同源物。这些观察结果提供了真核生物NADP+生物合成的见解,它在细胞和细胞器中具有关键作用。尽管NADP+在线粒体能量代谢中具有重要作用,但在人类线粒体中尚未发现能合成NADP+的NAD激酶。这些作者证明了C5orf33,一种动物和原生生物特有的蛋白质,是缺失的NAD激酶,并证明了它的线粒体定位和活性。
NAD kinase is the sole NADP+ biosynthetic enzyme. Despite the great significance of NADP+, to date no mitochondrial NAD kinase has been identified in human, and the source of human mitochondrial NADP+ remains elusive. Here we present evidence demonstrating that a human protein of unknown function, C5orf33, is a human mitochondrial NAD kinase; this protein likely represents the missing source of human mitochondrial NADP+. The C5orf33 protein exhibits NAD kinase activity, utilizing ATP or inorganic polyphosphate, and is localized in the mitochondria of human HEK293A cells. C5orf33 mRNA is more abundant than human cytosolic NAD kinase mRNA in almost all tissues examined. We further show by database searches that some animals and protists carry C5orf33 homologues as their sole NADP+ biosynthetic enzyme, whereas plants and fungi possess no C5orf33 homologue. These observations provide insights into eukaryotic NADP+ biosynthesis, which has pivotal roles in cells and organelles. Despite the central importance of NADP+ in mitochondrial energy metabolism, no NAD kinase has been found in human mitochondria to synthesize NADP+. These authors show C5orf33, a protein specific to animals and protists, to be the missing NAD kinase and demonstrate its mitochondrial localization and activity.
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