Functional diversity of complex I subunits in Candida albicans mitochondria.
Functional diversity of complex I subunits in Candida albicans mitochondria.
复制标题
白色念珠菌线粒体中复合物 I 亚基的功能多样性。
DOI：
10.1007/s00294-015-0518-6
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发表时间：
2016-02
期刊：
影响因子：
2.5
通讯作者：
Calderone R
中科院分区：
文献类型：
--
作者：
Li D;She X;Calderone R
我们的兴趣在白色念珠菌的线粒体已经取得了进展，以确定几个蛋白质是至关重要的复合物I（CI）的活动。我们推测哺乳动物和真菌线粒体CI在蛋白质水平上应该存在主要的功能差异。在我们追求这一想法的过程中，我们得到了来自广泛多样性物种的CI亚基蛋白的已发表数据的帮助，其中包括两种在哺乳动物中未发现的亚基蛋白。这些亚基蛋白被命名为Nuo 1 p和Nuo 2 p（NADH-泛醌氧化还原酶）。由于C.白色念珠菌蛋白是未知的，除了具有推定的NADH-氧化还原酶活性外，我们构建了可以与亲本细胞进行比较的敲除菌株。我们研究的相关性涉及这两种蛋白质在细胞生物学和发病机制中的关键作用以及它们在哺乳动物中的缺失。这些特点表明，它们可能被利用在抗真菌药物的发现。最初，我们的特点是Goa 1 p，显然调节CI活动，但不是CI亚基蛋白。我们使用goa 1 Δ与Nuo 1 p和Nuo 2 p进行比较。我们已经证明了这些蛋白质在维持CI活性、毒力和延长寿命方面的关键作用。最近，三种突变体和ndh 51 Δ（蛋白质是高度保守的Cl亚基）的转录谱分析已经揭示，存在重叠但也不同的功能分配，这表明亚基特异性。下面沿着描述了每种方法的差异和相似之处，以及我们解释这些数据的假设。我们的结论和观点是C.白色念珠菌C1亚基蛋白是高度保守的，除了定义非哺乳动物功能的两个。
Our interest in the mitochondria of Candida albicans has progressed to the identification of several proteins that are critical to complex I (CI) activity. We speculated that there should be major functional differences at the protein level between mammalian and fungal mitochondria CI. In our pursuit of this idea, we were helped by published data of CI subunit proteins from a broad diversity of species that included two subunit proteins that are not found in mammals. These subunit proteins have been designated as Nuo1p and Nuo2p (NADH-ubiquinone oxidoreductases). Since functional assignments of both C. albicans proteins were unknown, other than having a putative NADH-oxidoreductase activity, we constructed knock-out strains that could be compared to parental cells. The relevance of our research relates to the critical roles of both proteins in cell biology and pathogenesis and their absence in mammals. These features suggest they may be exploited in antifungal drug discovery. Initially, we characterized Goa1p that apparently regulates CI activity but is not a CI subunit protein. We have used the goa1Δ for comparisons to Nuo1p and Nuo2p. We have demonstrated the critical role of these proteins in maintaining CI activities, virulence, and prolonging life span. More recently, transcriptional profiling of the three mutants and an ndh51Δ (protein is a highly conserved CI subunit) has revealed that there are overlapping yet also different functional assignments that suggest subunit specificity. The differences and similarities of each are described below along with our hypotheses to explain these data. Our conclusion and perspective is that the C. albicans CI subunit proteins are highly conserved except for two that define non-mammalian functions.