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

Xueling Peng,Congcong Ma,Qilin Yu,Yuxin Feng,Mengsen Zhu,Mingchun Li,Biao Zhang,Tianyu Ma

doi:10.3390/molecules27030686

Abstract

Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase vip1 mediated synthesis of inositol heptakisphosphate (IP7) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of vip1 in Pi stress and lipid metabolism of Candida albicans has not yet been studied. We found that when vip1Δ/Δ was grown in glucose medium, if Pi was supplemented in the medium or mitochondrial Pi transporter was overexpressed in the strain, the lipid droplet (LD) content was reduced and membrane damage was alleviated. However, further studies showed that neither the addition of Pi nor the overexpression of the Pi transporter affected the energy balance of vip1Δ/Δ. In addition, the LD content of vip1Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of vip1Δ/Δ grown in PNMC was also lower than that grown in SC medium. This suggests that the increase in Pi demand by a high energy metabolic rate is the cause of LD accumulation in vip1Δ/Δ. In addition, in the vip1Δ/Δ strains, the core transcription factor PHO4 in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out vip1 completely blocks the activation of the PHO pathway, because the LD content of vip1Δ/Δ grown in the medium with β-glycerol phosphate as the Pi source was significantly reduced. In summary, the increased Pi demand and the decreased PHO pathway activity in vip1Δ/Δ ultimately lead to LD accumulation and cell membrane damage.

Highlights

Introduction iationsPi plays a role in many biological processes, such as cell signaling, energy metabolism, and phospholipid synthesis
Pi is of great significance in the process of energy metabolism, and it plays an important role in regulating three main energy production pathways: glycolysis, the tricarboxylic acid cycle (TCA) and oxidative phosphorylation [1,2]
For the first time, we confirm the connection between vip1 and the PHO pathway in C. albicans, and we further explore the correlation between energy metabolism and Pi supplementation

Summary

Introduction

Pi plays a role in many biological processes, such as cell signaling, energy metabolism, and phospholipid synthesis. Pi is of great significance in the process of energy metabolism, and it plays an important role in regulating three main energy production pathways: glycolysis, the tricarboxylic acid cycle (TCA) and oxidative phosphorylation [1,2]. Pi regulates glycolytic metabolism by regulating the activities of glyceraldehyde 3-phosphate dehydrogenase, hexokinase and phosphofructokinase; it regulates the entry of glutamine into the TCA cycle by regulating the activities of glutaminase and dehydrogenase, thereby controlling TCA metabolism; when it regulates oxidative phosphorylation, it acts as a substrate molecule in the process of ATP synthesis, and it can promote the activity of complex I in the electron transport chain and help the transfer of electrons from cytochrome b to cytochrome c [3,4].

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