Ddp1 Cooperates with Ppx1 to Counter a Stress Response Initiated by Nonvacuolar Polyphosphate

McCarthy, Liam; Abramchuk, Iryna; Wafy, Gamal; Denoncourt, Alix; Lavallée‐Adam, Mathieu; Downey, Michael

doi:10.1128/mbio.00390-22

Cited by 12 publications

(19 citation statements)

References 77 publications

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“…It was also demonstrated recently that it is the PolyP that accumulates outside the cell vacuole is the main factor of PolyP-mediated toxicity of elevated external Pi [25]. One can speculate that, mechanistically, the toxicity of extra-vacuolar short-chain PolyP can interfere with protein folding and/or matrix synthesis of biomolecules.…”

Section: Discussionmentioning

confidence: 97%

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Failure of <em>Micractinium simplicissimum </em>Phosphate Resilience upon Abrupt Re-Feeding of its Phosphorus-Starved Cultures

Лобакова¹,

Gorelova²,

Selyakh³

et al. 2023

Preprint

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Microalgae are naturally adapted to fluctuating availability of phosphorus (P) being capable to opportunistically uptake large amounts of inorganic phosphate (Pi) and safely store it in the cell as polyphosphate. Hence, many microalgal species are remarkably resilient to high concentrations of external Pi. Here we report on an exception from this pattern comprised by a failure of the high Pi-resilience in a strain Micractinium simplicissimum IPPAS C-2056 normally coping with a very high Pi concentrations. This phenomenon occurred after abrupt re-supplementation of Pi to the M. simplicissimum culture pre-starved of P. This was the case even if Pi was re-supplemented in a concentration far below the level toxic to the P-sufficient culture. We hypothesize that this effect can be mediated by a rapid formation of the potentially toxic short-chain polyphosphate following the mass influx of Pi into the P-starved cell. A possible reason for this is that the preceding P starvation impairs the capacity of the cell of converting the newly absorbed Pi into a “safe” storage form of long-chain polyphosphate. We believe that findings of this study can help to avoid sudden culture crashes, they are also of potential significance for development of algae-based technologies for efficient bioremoval of P from P-rich waste streams.

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Section: Discussionmentioning

confidence: 97%

“…Nevertheless, there are reports on the toxicity of exogenic Pi to microalgae [23][24][25] although the mechanisms of this phenomenon a far from being understood. Still, understanding of P toxicity is important e.g.…”

Section: Introductionmentioning

confidence: 99%

Failure of <em>Micractinium simplicissimum </em>Phosphate Resilience upon Abrupt Re-Feeding of its Phosphorus-Starved Cultures

Лобакова¹,

Gorelova²,

Selyakh³

et al. 2023

Preprint

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“…Expression of E. coli PPK in human cells results in the synthesis of high levels of polyP throughout the cell [122,123]. In yeast, this results in toxicity due to accumulation of polyP outside of the vacuole [18,25]. two shorter chains, or cleave terminal bonds to release a single inorganic phosphate [34,35].…”

Section: Ppn1mentioning

confidence: 99%

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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“…The VTC complex is not only a polyP polymerase but also a polyP translocase. To avoid the toxicity of the accumulation of polyP in the cytoplasm, polyP synthesis and the immediate translocation of polyP into the vacuole are coupled (Gerasimaite, Sharma et al, 2014, McCarthy, Abramchuk et al, 2022). However, how they are coupled remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Cryo-EM structure of the polyphosphate polymerase VTC: Coupling polymer synthesis to membrane transit

Liu

Wang

Comte‐Miserez

et al. 2023

Preprint

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The eukaryotic polyphosphate (polyP) polymerase VTC complex synthesizes polyP from adenosine triphosphate (ATP) and translocates polyP across the vacuolar membrane to maintain an intracellular phosphate (Pi) homeostasis. To discover how VTC complex solves this fundamental aspect, we determined a cryo-electron microscopy structure of an endogenous VTC complex (Vtc4/Vtc3/Vtc1) from Saccharomyces cerevisiae at 3.1 A resolution. The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3 and three Vtc1 subunits. The transmembrane region forms a polyP selective channel, probably adopting a resting state conformation, in which a latch-like, horizonal helix of Vtc4 limits the entrance. The catalytic Vtc4 central domain locates on top of the pseudo-symmetric polyP channel, creating a strongly electropositive pathway for nascent polyP that can couple synthesis to translocation. The SPX domain of Vtc4 positively regulates polyP synthesis and regulation of VTC complex. The non-catalytic Vtc3 regulates VTC through a phoshorylatable loop. Our findings, along with the functional data, allow us to propose a mechanism of polyP channel gating and VTC complex activation.

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Ddp1 Cooperates with Ppx1 to Counter a Stress Response Initiated by Nonvacuolar Polyphosphate

Abstract: Cells from bacteria to humans have a molecule called polyphosphate (polyP) that functions in diverse processes. In many microbes, polyP is sequestered in granules or lysosome-related organelles such as vacuoles.

Cited by 12 publications

References 77 publications

Failure of <em>Micractinium simplicissimum </em>Phosphate Resilience upon Abrupt Re-Feeding of its Phosphorus-Starved Cultures

Failure of <em>Micractinium simplicissimum </em>Phosphate Resilience upon Abrupt Re-Feeding of its Phosphorus-Starved Cultures

The emerging landscape of eukaryotic polyphosphatases

Cryo-EM structure of the polyphosphate polymerase VTC: Coupling polymer synthesis to membrane transit

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