Enzymes of yeast polyphosphate metabolism: structure, enzymology and biological roles

Gerasimaitė, Rūta; Mayer, Andreas

doi:10.1042/bst20150213

Cited by 55 publications

(64 citation statements)

References 52 publications

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“…Due to its structural incorporation into nucleic acids and phospholipids as well as roles in protein modification and signal transduction, phosphorus is an essential element for sustaining life [37]. In yeast, phosphorus is primarily stored as chains of inorganic polyphosphate (polyP), most of which is retained in the vacuole [37][38][39][40]. Aside from acting as a phosphate storage mechanism, polyP functions in metal chelation in yeast, whereas in mammals it serves diverse functions ranging from activation of inflammatory responses and blood clotting to regulation of bone calcification [40].…”

Section: Polyphosphatementioning

confidence: 99%

“…In yeast, polyP is simultaneously synthesized and translocated across the vacuolar membrane by the vacuolar transporter chaperone (VTC) complex, which consists of 2 proposed regulatory subunits, Vtc1 and Vtc2 or Vtc3, and the catalytic subunit Vtc4 [40][41][42]. The VTC complex can form 2 distinct subcomplexes; the first consists of Vtc1, Vtc3, and Vtc4, and localizes primarily to the vacuolar membrane, whereas the second, consisting of Vtc1, Vtc2, and Vtc4, localizes to the cell periphery, but can be found at the vacuole during phosphate starvation [40]. Vtc4 synthesizes polyP from ATP in a metal ion-dependent manner, with Mn 2+ being the most effective cofactor.…”

Section: Polyphosphatementioning

confidence: 99%

“…PolyP within the vacuole can be broken down by the polyphosphatase Ppn1 [40], and the expression of this enzyme increases during phosphate starvation [45]. Ppn1 transits to the vacuole via the multivesicular body (MVB) pathway, after which the N-terminal transmembrane domain is cleaved, releasing the soluble enzyme into the vacuole lumen [46].…”

Section: Polyphosphatementioning

confidence: 99%

See 2 more Smart Citations

Vacuolar hydrolysis and efflux: current knowledge and unanswered questions

Parzych

Klionsky

2018

Autophagy

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Hydrolysis within the vacuole in yeast and the lysosome in mammals is required for the degradation and recycling of a multitude of substrates, many of which are delivered to the vacuole/lysosome by autophagy. In humans, defects in lysosomal hydrolysis and efflux can have devastating consequences, and contribute to a class of diseases referred to as lysosomal storage disorders. Despite the importance of these processes, many of the proteins and regulatory mechanisms involved in hydrolysis and efflux are poorly understood. In this review, we describe our current knowledge of the vacuolar/lysosomal degradation and efflux of a vast array of substrates, focusing primarily on what is known in the yeast Saccharomyces cerevisiae. We also highlight many unanswered questions, the answers to which may lead to new advances in the treatment of lysosomal storage disorders.

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Section: Polyphosphatementioning

confidence: 99%

Section: Polyphosphatementioning

confidence: 99%

Section: Polyphosphatementioning

confidence: 99%

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Vacuolar hydrolysis and efflux: current knowledge and unanswered questions

Parzych

Klionsky

2018

Autophagy

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“…Extreme phosphate-limited growth of S. cerevisiae induces expression of PHO84 , which encodes a high-affinity phosphate/proton symporter and vacuolar synthesis of inorganic polyphosphate(41). By acting as a phosphorus sink, polyphosphate sustains phosphate uptake at low extracellular concentrations (41, 42). Its synthesis in yeast requires activity of the vacuolar H+-ATPase (V-ATPase) to maintain a proton-motive force across the vacuolar membrane (41).…”

Section: Discussionmentioning

confidence: 99%

Quantitative physiology of non-energy-limited retentostat cultures ofSaccharomyces cerevisiaeat near-zero specific growth rates

Liu

Masoudi

Pronk

et al. 2019

Preprint

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excess 12 13 14 15 16 17 18 19 20 21 a Current address: Royal Haskoning DHV, George Hintzenweg 85, 3009 AM Rotterdam, The Netherlands.prevent loss of feedstock to biomass production. Establishing S. cerevisiae cultures in which 46 growth is restricted by the limited supply of a non-energy substrate could therefore have a 47 wide range of industrial applications, but remains largely unexplored. In this work we 48 accomplished near-zero growth of S. cerevisiae through limited supply of a non-energy 49 nutrient, namely the nitrogen or phosphorus source and carried out a quantitative 50 physiology study of the cells under these conditions. The possibility to achieve near-zero-51 growth S. cerevisiae cultures through limited supply of a non-energy nutrient may offer 52 interesting prospects to develop novel fermentation processes for high-yield production of 53 bio-based chemicals. 54 Growth and viability in ammonium-and phosphate-limited retentostat cultures130 Retentostat cultures were started by redirecting the effluent of steady-state ammonium-or 131 phosphate-limited chemostat cultures, grown at a dilution rate of 0.025 h -1 , through a 132 membrane filter unit placed inside the reactor (see Materials and Methods). Replicate 133 ammonium-limited retentostats were operated for 220 h with full biomass retention, after 134 which fouling caused the membrane filters to clog. Membrane fouling was not observed in 135 the phosphate-limited retentostats, which were operated with full biomass retention until, 136 after 400 h, the biomass concentration had reached a stable value. 137

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“…PolyP is translocated into the vacuole as it is synthesized (Gerasimaitė et al, 2014), where it accumulates to remarkably high levels (>200 mM total cellular concentration, comprising up to 10% of the dry weight of the cell) (Auesukaree et al, 2004;Kornberg et al, 1999). Lower levels of polyP can be found in other subcellular compartments including the cytoplasm, nucleus, plasma membrane and mitochondria (Gerasimaitė and Mayer, 2016;Lichko et al, 2006). How polyP localizes to these areas of the cell is not understood.…”

Section: Introductionmentioning

confidence: 99%

A broad response to intracellular long-chain polyphosphate in human cells

Bondy‐Chorney

Abramchuk

Nasser

et al. 2020

Preprint

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Polyphosphates (PolyP) are composed of long chains of inorganic phosphates linked together by phosphoanhydride bonds. They are found in all kingdoms of life, playing roles in cell growth, infection, and blood coagulation. A resurgence in interest in polyP has shown links to diverse aspects of human disease. However, unlike in bacteria and lower eukaryotes, the mammalian enzymes responsible for polyP metabolism are not known. Many studies have resorted to adding polyP to cell culture media, but it is not clear if externally applied polyP enters the cell to impact signaling events or whether their effect is mediated exclusively by extracellular receptors. For the first time, we use RNA-seq and mass spectrometry to define a broad impact of polyP produced inside of mammalian cells via ectopic expression of the E. coli polyP synthetase Ppk1. RNA-seq demonstrates that Ppk1 expression impacts expression of over 350 genes enriched for processes related to transcription and cell motility. Analysis of proteins via label-free mass spectrometry identified over 100 changes with functional enrichment in cell migration. Follow up work suggests a role for internally-synthesized polyP in promoting activation of mTOR and ERK1/2-EGR1 signaling pathways implicated in cell growth and stress. Finally, fractionation analysis shows that polyP accumulated in multiple cellular compartments and was associated with the relocalization several nuclear/cytoskeleton proteins, including chromatin bound proteins DEK, TAF10, GTF2I and translation initiation factor eIF5b. Our work is the first to demonstrate that internally produced polyP can activate diverse signaling pathways in human cells.Significance StatementFor many years following its discovery in 1890, polyphosphates (polyP) were dismissed as evolutionary fossils. Best understood for its role in bacteria and yeast, our understanding of polyP in mammals remains rudimentary because the enzymes that synthesize and degrade polyP in mammalian systems are currently unknown. In our work, we carried out large-scale transcriptome and proteome approaches on human cells designed to accumulate internally produced polyP via ectopic expression of a bacterial polyP synthetase. Our work is the first to systematically assess the impact of increased intracellular polyP.

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Enzymes of yeast polyphosphate metabolism: structure, enzymology and biological roles

Cited by 55 publications

References 52 publications

Vacuolar hydrolysis and efflux: current knowledge and unanswered questions

Vacuolar hydrolysis and efflux: current knowledge and unanswered questions

Quantitative physiology of non-energy-limited retentostat cultures ofSaccharomyces cerevisiaeat near-zero specific growth rates

A broad response to intracellular long-chain polyphosphate in human cells

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