Model systems for studying polyphosphate biology: a focus on microorganisms

Denoncourt, Alix; Downey, Michael

doi:10.1007/s00294-020-01148-x

Cited by 26 publications

(55 citation statements)

References 178 publications

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“…For example, in the brain polyP chains are ≈800 Pi units, [ 58 ] similar in length to those produced by many bacteria. [ 1 ]…”

Section: Promises and Challengesmentioning

confidence: 99%

“…In bacteria, polyP is synthesized by conserved polyphosphate kinases (PPK1 and/or PPK2), which use adenosine triphosphate (ATP) or guanosine triphosphate (GTP) molecules as substrates. [1,2] In many bacteria, polyP is not constitutively present but accumulates rapidly in response to stresses. [1] On the other hand, polyP accumulation is countered by the action of polyphosphatases.…”

Section: Polyphosphate-a Ubiquitous "Jack Of All Trades"mentioning

confidence: 99%

“…[1,2] In many bacteria, polyP is not constitutively present but accumulates rapidly in response to stresses. [1] On the other hand, polyP accumulation is countered by the action of polyphosphatases. [1] For example, Escherichia coli PPX is an exopolyphosphatase that degrades long polyP chains starting at the end of the chain.…”

Section: Polyphosphate-a Ubiquitous "Jack Of All Trades"mentioning

confidence: 99%

“…[56,57] Nevertheless, these assays are readily applied to microorganisms such as E. coli and yeast because these species accumulate polyP chains to very high cellular concentrations (20 and >200 mM, respectively, customarily expressed in terms of phosphate monomers). [1] In contrast, polyP concentrations are lower in mammalian cells, and in some cases, may be very close to the threshold of detection, at least for commonly applied assays. In some studies, this may be compounded by degradation of polyP in response to cell death or during extraction.…”

Section: The Highs and The Lows-linking Polyp Concentration To Lysine Polyphosphorylationmentioning

confidence: 99%

“…[ 1 ] On the other hand, polyP accumulation is countered by the action of polyphosphatases. [ 1 ] For example, Escherichia coli PPX is an exopolyphosphatase that degrades long polyP chains starting at the end of the chain. [ 3 ] In the budding yeast Saccharomyces cerevisiae , polyP is synthesized by the vacuolar transporter chaperone (VTC) complex at the vacuolar membrane, [ 4 ] prior to being stored at high levels (200 mM total cellular concentration, in terms of individual Pi units) in the vacuole lumen.…”

Section: Introductionmentioning

confidence: 99%

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The promises of lysine polyphosphorylation as a regulatory modification in mammals are tempered by conceptual and technical challenges

Baijal

Downey

2021

BioEssays

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Polyphosphate (polyP) is a ubiquitous biomolecule thought to be present in all cells on Earth. PolyP is deceivingly simple, consisting of repeated units of inorganic phosphates polymerized in long energy‐rich chains. PolyP is involved in diverse functions in mammalian systems—from cell signaling to blood clotting. One exciting avenue of research is a new nonenzymatic post‐translational modification, termed lysine polyphosphorylation, wherein polyP chains are covalently attached to lysine residues of target proteins. While the modification was first characterized in budding yeast, recent work has now identified the first human targets. There is significant promise in this area of biomedical research, but a number of technical issues and knowledge gaps present challenges to rapid progress. In this review, the current state of the field is summarized and existing roadblocks related to the study of lysine polyphosphorylation in higher eukaryotes are introduced. It is discussed how limited methods to identify targets of polyphosphorylation are further impacted by low concentration, unknown regulatory enzymes, and sequestration of polyP into compartments in mammalian systems. Furthermore, suggestions on how these obstacles could be addressed or what their physiological relevance may be within mammalian cells are presented.

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“…For example, in the brain polyP chains are ≈800 Pi units, [ 58 ] similar in length to those produced by many bacteria. [ 1 ]…”

Section: Promises and Challengesmentioning

confidence: 99%

Section: Polyphosphate-a Ubiquitous "Jack Of All Trades"mentioning

confidence: 99%

Section: Polyphosphate-a Ubiquitous "Jack Of All Trades"mentioning

confidence: 99%

Section: The Highs and The Lows-linking Polyp Concentration To Lysine Polyphosphorylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The promises of lysine polyphosphorylation as a regulatory modification in mammals are tempered by conceptual and technical challenges

Baijal

Downey

2021

BioEssays

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The emerging landscape of eukaryotic polyphosphatases

McCarthy

Downey

2023

FEBS Letters

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Polyphosphate (polyP) is a conserved polymer of inorganic phosphate residues that can reach thousands of moieties in length. PolyP has been implicated in cellular functions ranging from energy and phosphate homeostasis to cell signalling in eukaryotes from yeast to humans. Despite the interest in the role of polyP as a signalling molecule, the spatiotemporal regulation of polyP itself remains poorly understood. This knowledge gap limits our ability to understand how polyP impacts the physiology of normal and diseased cells and how this might be exploited in a therapeutic context. Polyphosphatases, enzymes that degrade polyP to generate shorter chains and free inorganic phosphate are ideally positioned to mediate polyP dynamics. However, little is known about how the activities of these enzymes are linked to specific cellular functions and how they might be regulated. Here, we provide an indepth overview of polyphosphatase enzymes in budding yeast, which has served as a workhorse for polyP research, and in mammalian cells where the enzymes that make and degrade polyP have remained elusive. We identify critical open questions in both systems and propose strategies to guide future work.

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Inorganic Polyphosphate, Mitochondria, and Neurodegeneration

Urquiza

Solesio

2022

Inorganic Polyphosphates

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Model systems for studying polyphosphate biology: a focus on microorganisms

Cited by 26 publications

References 178 publications

The promises of lysine polyphosphorylation as a regulatory modification in mammals are tempered by conceptual and technical challenges

The promises of lysine polyphosphorylation as a regulatory modification in mammals are tempered by conceptual and technical challenges

The emerging landscape of eukaryotic polyphosphatases

Inorganic Polyphosphate, Mitochondria, and Neurodegeneration

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