Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage

Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase <i>vip1</i> mediated synthesis of inositol heptakisphosphate (IP<sub>7</sub>) regulates the phosphate-responsive (...

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Main Authors: Xueling Peng, Congcong Ma, Yuxin Feng, Biao Zhang, Mengsen Zhu, Tianyu Ma, Qilin Yu, Mingchun Li
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/3/686
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author Xueling Peng
Congcong Ma
Yuxin Feng
Biao Zhang
Mengsen Zhu
Tianyu Ma
Qilin Yu
Mingchun Li
author_facet Xueling Peng
Congcong Ma
Yuxin Feng
Biao Zhang
Mengsen Zhu
Tianyu Ma
Qilin Yu
Mingchun Li
author_sort Xueling Peng
collection DOAJ
description Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase <i>vip1</i> mediated synthesis of inositol heptakisphosphate (IP<sub>7</sub>) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of <i>vip1</i> in Pi stress and lipid metabolism of <i>Candida albicans</i> has not yet been studied. We found that when <i>vip1</i>Δ/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 <i>vip1</i>Δ/Δ. In addition, the LD content of <i>vip1</i>Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of <i>vip1</i>Δ/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 <i>vip1</i>Δ/Δ. In addition, in the <i>vip1</i>Δ/Δ strains, the core transcription factor <i>PHO4</i> in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out <i>vip1</i> completely blocks the activation of the PHO pathway, because the LD content of <i>vip1</i>Δ/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 <i>vip1</i>Δ/Δ ultimately lead to LD accumulation and cell membrane damage.
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spelling doaj.art-3e89b6d9fbfe4f2e9d8e5838348d0d282023-11-23T17:10:50ZengMDPI AGMolecules1420-30492022-01-0127368610.3390/molecules27030686Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane DamageXueling Peng0Congcong Ma1Yuxin Feng2Biao Zhang3Mengsen Zhu4Tianyu Ma5Qilin Yu6Mingchun Li7Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300457, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300457, ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaPhosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase <i>vip1</i> mediated synthesis of inositol heptakisphosphate (IP<sub>7</sub>) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of <i>vip1</i> in Pi stress and lipid metabolism of <i>Candida albicans</i> has not yet been studied. We found that when <i>vip1</i>Δ/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 <i>vip1</i>Δ/Δ. In addition, the LD content of <i>vip1</i>Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of <i>vip1</i>Δ/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 <i>vip1</i>Δ/Δ. In addition, in the <i>vip1</i>Δ/Δ strains, the core transcription factor <i>PHO4</i> in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out <i>vip1</i> completely blocks the activation of the PHO pathway, because the LD content of <i>vip1</i>Δ/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 <i>vip1</i>Δ/Δ ultimately lead to LD accumulation and cell membrane damage.https://www.mdpi.com/1420-3049/27/3/686PHO pathwayphosphate stresslipid droplet
spellingShingle Xueling Peng
Congcong Ma
Yuxin Feng
Biao Zhang
Mengsen Zhu
Tianyu Ma
Qilin Yu
Mingchun Li
Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage
Molecules
PHO pathway
phosphate stress
lipid droplet
title Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage
title_full Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage
title_fullStr Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage
title_full_unstemmed Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage
title_short Phosphate Starvation by Energy Metabolism Disturbance in <i>Candida albicans</i><i>vip1</i>Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage
title_sort phosphate starvation by energy metabolism disturbance in i candida albicans i i vip1 i δ δ induces lipid droplet accumulation and cell membrane damage
topic PHO pathway
phosphate stress
lipid droplet
url https://www.mdpi.com/1420-3049/27/3/686
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