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Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation

Cells stabilize intracellular inorganic phosphate (P(i)) to compromise between large biosynthetic needs and detrimental bioenergetic effects of P(i). P(i) homeostasis in eukaryotes uses Syg1/Pho81/Xpr1 (SPX) domains, which are receptors for inositol pyrophosphates. We explored how polymerization and...

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Autores principales: Kim, Geun-Don, Qiu, Danye, Jessen, Henning Jacob, Mayer, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294617/
https://www.ncbi.nlm.nih.gov/pubmed/37074217
http://dx.doi.org/10.1128/mbio.00102-23
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author Kim, Geun-Don
Qiu, Danye
Jessen, Henning Jacob
Mayer, Andreas
author_facet Kim, Geun-Don
Qiu, Danye
Jessen, Henning Jacob
Mayer, Andreas
author_sort Kim, Geun-Don
collection PubMed
description Cells stabilize intracellular inorganic phosphate (P(i)) to compromise between large biosynthetic needs and detrimental bioenergetic effects of P(i). P(i) homeostasis in eukaryotes uses Syg1/Pho81/Xpr1 (SPX) domains, which are receptors for inositol pyrophosphates. We explored how polymerization and storage of P(i) in acidocalcisome-like vacuoles supports Saccharomyces cerevisiae metabolism and how these cells recognize P(i) scarcity. Whereas P(i) starvation affects numerous metabolic pathways, beginning P(i) scarcity affects few metabolites. These include inositol pyrophosphates and ATP, a low-affinity substrate for inositol pyrophosphate-synthesizing kinases. Declining ATP and inositol pyrophosphates may thus be indicators of impending P(i) limitation. Actual P(i) starvation triggers accumulation of the purine synthesis intermediate 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which activates P(i)-dependent transcription factors. Cells lacking inorganic polyphosphate show P(i) starvation features already under P(i)-replete conditions, suggesting that vacuolar polyphosphate supplies P(i) for metabolism even when P(i) is abundant. However, polyphosphate deficiency also generates unique metabolic changes that are not observed in starving wild-type cells. Polyphosphate in acidocalcisome-like vacuoles may hence be more than a global phosphate reserve and channel P(i) to preferred cellular processes.
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spelling pubmed-102946172023-06-28 Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation Kim, Geun-Don Qiu, Danye Jessen, Henning Jacob Mayer, Andreas mBio Research Article Cells stabilize intracellular inorganic phosphate (P(i)) to compromise between large biosynthetic needs and detrimental bioenergetic effects of P(i). P(i) homeostasis in eukaryotes uses Syg1/Pho81/Xpr1 (SPX) domains, which are receptors for inositol pyrophosphates. We explored how polymerization and storage of P(i) in acidocalcisome-like vacuoles supports Saccharomyces cerevisiae metabolism and how these cells recognize P(i) scarcity. Whereas P(i) starvation affects numerous metabolic pathways, beginning P(i) scarcity affects few metabolites. These include inositol pyrophosphates and ATP, a low-affinity substrate for inositol pyrophosphate-synthesizing kinases. Declining ATP and inositol pyrophosphates may thus be indicators of impending P(i) limitation. Actual P(i) starvation triggers accumulation of the purine synthesis intermediate 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which activates P(i)-dependent transcription factors. Cells lacking inorganic polyphosphate show P(i) starvation features already under P(i)-replete conditions, suggesting that vacuolar polyphosphate supplies P(i) for metabolism even when P(i) is abundant. However, polyphosphate deficiency also generates unique metabolic changes that are not observed in starving wild-type cells. Polyphosphate in acidocalcisome-like vacuoles may hence be more than a global phosphate reserve and channel P(i) to preferred cellular processes. American Society for Microbiology 2023-04-19 /pmc/articles/PMC10294617/ /pubmed/37074217 http://dx.doi.org/10.1128/mbio.00102-23 Text en Copyright © 2023 Kim et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Kim, Geun-Don
Qiu, Danye
Jessen, Henning Jacob
Mayer, Andreas
Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation
title Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation
title_full Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation
title_fullStr Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation
title_full_unstemmed Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation
title_short Metabolic Consequences of Polyphosphate Synthesis and Imminent Phosphate Limitation
title_sort metabolic consequences of polyphosphate synthesis and imminent phosphate limitation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294617/
https://www.ncbi.nlm.nih.gov/pubmed/37074217
http://dx.doi.org/10.1128/mbio.00102-23
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