Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Science, Nankai University, No. 94, Weijin Road, Tianjin 300071, P. R. China.
FEMS Yeast Res. 2020 Sep 1;20(6). doi: 10.1093/femsyr/foaa050.
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.
肌醇多磷酸盐（IPs）是一类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。肌醇多磷酸激酶是 IPs 产生和转化的关键酶，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，我们鉴定了白色念珠菌中的肌醇多磷酸激酶 Ipk1，并发现它定位于细胞核中。此外，在 ipk1Δ/Δ 突变体中，线粒体呼吸链复合物的活性和线粒体功能严重受损，这与转录谱分析显示的线粒体功能相关基因下调有关。ipk1Δ/Δ 突变体还表现出对一系列环境应激的敏感性，如抗真菌药物、氧化剂、细胞壁破坏剂和巨噬细胞攻击，随后在小鼠系统性感染模型中的毒力减弱。这些发现首次报道了肌醇多磷酸激酶 Ipk1 在白色念珠菌中的重要性，特别是其在维持线粒体功能和致病性方面的作用。
