Study on the Function of the Inositol Polyphosphate Kinases Kcs1 and Vip1 of Candida albicans in Energy Metabolism

Abstract

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.

Phosphate Starvation by Energy Metabolism Disturbance in Candida albicansvip1Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage

“…C. albicans vip1 knockout reduces the growth rate of strain in glucose medium and accumulates a large number of LDs [ 11 ]. If Pi was added to the medium, it was found that supplementation Pi could reduce the LD content in the vip1 Δ/Δ strain ( Figure 1 A).…”

“…Our previous research found that the increase in the glycolytic rate of C. albicans vip1 Δ/Δ accompanied by a decrease in mitochondrial activity was the cause of LD accumulation. Drug interference or plasmid overexpression was used to disturb energy balance to affect LD accumulation [ 11 ]. Because the content of Pi affects the energy balance, and energy metabolism disorder in C. albicans vip1 Δ/Δ is the cause of LD accumulation, we asked, in C. albicans vip1 Δ/Δ, whether Pi-regulated LD accumulation is achieved by affecting the energy balance.…”

“…C. albicans KCS1 knockout does not affect the energy metabolism of the strain, while vip1 knockout results in increased glycolysis; the mitochondria of the strain are not damaged by vip1 knockout, but when the strain is grown in glucose medium, increased glycolysis with reduced mitochondrial activity is the cause of LD accumulation [ 11 ]. The high glycolysis rate of C. albicans in glucose medium caused by vip1 knockout is the reason for the energy imbalance.…”

“…Regarding the phenomenon that Pi supplementation can help vip1 Δ/Δ resist membrane damage stimulation, we propose two hypotheses: Firstly, we have previously found that membrane damage in vip1 Δ/Δ is positively correlated with LD accumulation because the accumulation of LDs causes an increase in intracellular osmotic pressure. To prevent the cell from swelling and rupturing, an increase in chitin content promotes cell wall thickening and thus leads to membrane damage [ 11 ]. In this experiment, the content of LDs in vip1 Δ/Δ decreased and the properties of the cell membrane improved after the addition of Pi.…”

Inositol polyphosphate–protein interactions: Implications for microbial pathogenicity

“…The glycolysis-skewed metabolism was compensated for by an accumulation of lipid droplets (Peng et al, 2020). Only the vip1ΔΔ mutant accumulated cell wall chitin and exhibited plasma membrane leakage which eventually led to death.…”