The inositol polyphosphate kinase Ipk1 transcriptionally regulates mitochondrial functions in Candida albicans
The inositol polyphosphate kinase Ipk1 transcriptionally regulates mitochondrial functions in Candida albicans
复制标题
肌醇多磷酸激酶 Ipk1 转录调节白色念珠菌的线粒体功能
DOI：
10.1093/femsyr/foaa050
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发表时间：
2020
影响因子：
3.2
通讯作者：
Mingchun Li
中科院分区：
文献类型：
--
作者：
Hangqi Zhu;Nali Zhu;Liping Peng;Bing Zhang;Qilin Yu;Mingchun Li
肌醇多聚磷酸盐(IPs)是一类重要的信号分子家族，调节着染色质重塑、转录和mRNA输出等多种细胞过程。肌醇多磷酸酶作为产生和转化IP的关键酶，直接决定着细胞内IP的水平，因此参与了许多细胞过程。然而，它在人类主要真菌病原体--白色念珠菌中的作用仍有待研究。在本研究中，我们鉴定了肌醇多磷酸激酶Ipk1 Inc.白念珠菌发现它定位在细胞核中。此外，在ipk1Δ/Δ突变体中，线粒体呼吸链复合体的活性和线粒体功能严重受损，这与转录图谱分析显示的线粒体功能相关基因的下调有关。在小鼠系统感染模型中，IPK1Δ/Δ突变体还表现出对一系列环境应激的超敏反应，如抗真菌药物、氧化剂、细胞壁干扰剂和巨噬细胞攻击，随后毒力减弱。这些发现首次报道了肌醇多磷酸激酶Ipk1 Inc.的重要性。白念珠菌，特别是它在维持线粒体功能和致病性方面的作用。
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 inCandida albicans, the leading fungal pathogen in human beings, remain to be investigated. In this study, we identified the inositol polyphosphate kinase Ipk1 inC. albicansand found that it localizes in the nucleus. Moreover, in theipk1Δ/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. Theipk1Δ/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 inC. albicans, especially its role in mitochondrial function maintenance and pathogenicity.