Inositol polyphosphates (IPs) is an important family of signaling molecules that regulate multiple cellular processes, such as chromatin remodeling, transcription and mRNA export. Inositol polyphosphate kinases, as the critical enzymes for production and transformation of IPs, directly determine the intracellular levels of IPs and therefore are involved in many cellular processes. However, its roles in Candida albicans, the leading fungal pathogen in human beings, remain to be investigated. In this study, we identified the inositol polyphosphate kinase Ipk1 in C. albicans and found that it localizes in the nucleus. Moreover, in the ipk1Δ/Δ mutant, the activity of mitochondrial respiratory chain complexes and the mitochondrial function was severely impaired, which were associated with down-regulation of mitochondrial function-related genes revealed by transcription profiling analysis. The ipk1Δ/Δ mutant also displayed hypersensitivity to a series of environmental stresses, such as antifungal drugs, oxidants, cell wall perturbing agents and macrophage attacks, followed by attenuation of virulence in a mouse systematic infection model. These findings firstly reported the importance of inositol polyphosphate kinase Ipk1 in C. albicans, especially its role in mitochondrial function maintenance and pathogenicity.

中文翻译：

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肌醇多磷酸激酶 Ipk1 转录调节白色念珠菌的线粒体功能。

多磷酸肌醇 (IP) 是一个重要的信号分子家族，可调节多种细胞过程，如染色质重塑、转录和 mRNA 输出。肌醇多磷酸激酶作为 IPs 生产和转化的关键酶，直接决定 IPs 的细胞内水平，因此参与许多细胞过程。然而，其在人类主要真菌病原体白色念珠菌中的作用仍有待研究。在这项研究中，我们在白色念珠菌中鉴定了肌醇多磷酸激酶 Ipk1，并发现它位于细胞核中。此外，在ipk1Δ/Δ 突变体，线粒体呼吸链复合物的活性和线粒体功能严重受损，这与转录谱分析揭示的线粒体功能相关基因的下调有关。所述IPK1 Δ/Δ的突变体也显示过敏症的一系列环境胁迫，如抗真菌药，氧化剂，细胞壁扰动剂和巨噬细胞的攻击，然后在小鼠全身感染模型的毒力的衰减。这些发现首先报道了肌醇多磷酸激酶 Ipk1 在白色念珠菌中的重要性，特别是其在线粒体功能维持和致病性中的作用。