Inositol polyphosphates are a family of inositol derivatives and ubiquitously distributed in various organisms. Their generation is catalyzed by inositol polyphosphate multikinases, which play essential roles in abundant cellular processes. However, little is known about the kinds and functions of inositol polyphosphate multikinases in the important fungal pathogen, C. albicans. In this study, we identified a C. albicans inositol polyphosphate multikinase, Ipk2. This kinase shares the conserved IPK domain and localizes in the nucleus. A strain with controllable expression of IPK2 was constructed using the inducible promoter of MET3. Down-regulation of IPK2 by addition of methionine and cysteine enhanced the ability of hyphal development, increased expression of hypha-specific genes and promoted transport of hypha-specific factors. Moreover, this down-regulation rendered increase in cytoplasmic calcium levels but decrease in cellular total calcium contents, indicating its role in regulation of calcium homeostasis. Assays of secretion and macrophage killing further demonstrated that Ipk2 negatively regulated secretion of degradative enzymes and damage to macrophages. This study sheds a novel light on the functions of inositol polyphosphate multikinases in fungal organisms.

No abstract

Apoptosis-inducing factor (AIF) is a conserved flavoprotein localized in the mitochondria, inducing apoptosis after translocation into the nucleus. However, its role in the important fungal pathogen, Candida albicans, remains to be investigated. In this study, we find that the C. albicans AIF protein Aif1, similar to its homologues in other organisms, is localized at the mitochondria and translocated into the nucleus under apoptosis-inducing conditions. Moreover, deletion of AIF1 causes attenuated apoptosis in this pathogen under apoptosis-inducing conditions, such as the treatment of 2 mm H2 O2 , 10 mm acetic acid or 0.08 mg/l caspofungin, and its overexpression enhances this process. Interestingly, treatment with high levels of these agents leads to reversed sensitivity of aif1Δ/Δ and the overexpression strain AIF1ov. In addition, the virulence of C. albicans is not affected by deletion or overexpression of AIF1. Hence, C. albicans Aif1, as a mitochondria-localized protein, plays a dual role in the regulation of cell death under different concentrations of the stress-caused agents. Copyright © 2016 John Wiley & Sons, Ltd.

In Saccharomyces cerevisiae, inositol polyphosphate kinase KCS1 but not VIP1 knockout is of great significance for maintaining cell viability, promoting glycolysis metabolism, and inducing mitochondrial damage. The functions of Candida albicans inositol polyphosphate kinases Kcs1 and Vip1 have not yet been studied. In this study, we found that the growth rate of C. albicans vip1Δ/Δ strain in glucose medium was reduced and the upregulation of glycolysis was accompanied by a decrease in mitochondrial activity, resulting in a large accumulation of lipid droplets, along with an increase in cell wall chitin and cell membrane permeability, eventually leading to cell death. Relieving intracellular glycolysis rate or increasing mitochondrial metabolism can reduce lipid droplet accumulation, causing a reduction in chitin content and cell membrane permeability. The growth activity and energy metabolism of the vip1Δ/Δ strains in a non-fermentable carbon source glycerol medium were not different from those of the wild-type strains, indicating that knocking out VIP1 did not cause mitochondria damage. Moreover, C. albicans KCS1 knockout did not affect cell activity and energy metabolism. Thus, in C. albicans, Vip1 is more important than Kcs1 in regulating cell viability and energy metabolism.

No abstract