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Biomolecules
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Polyphosphate (PolyP) in Health and Disease
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Polyphosphate (PolyP) in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-derived Molecules".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 3156

Special Issue Editor

Dr. Félix A. Ruiz

E-Mail Website
Guest Editor
Department of Biomedicine, Biotechnology, and Public Health, Medical School, Universidad de Cadiz, 11003 Cadiz, Spain
Interests: polyphosphate; polyP; polymer; phosphate
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inorganic polyphosphate (polyP), a linear polymer of orthophosphate residues, is a ubiquitous molecule with increasingly recognized roles in health and disease. Recent discoveries of the implications of polyP in physiological and pathological processes such as bioenergetics, inflammation, neurodegeneration, cardiovascular disorders, and cancer, among others, are currently being explored, so there is a need to improve and accelerate the dissemination of this new knowledge. As novel methodologies progress in our ability to detect, manipulate, and quantify polyP, new insights into its functions are being uncovered. However, this field still has significant knowledge gaps, particularly concerning the interplay between polyP molecular roles and disease pathophysiology. This Special Issue of Biomolecules aims to highlight recent advances in polyP research, focusing on its functions, physiological relevance, and contribution to disease mechanisms. Original research articles, methodological advances, and comprehensive reviews that expand our understanding of polyP biology and its potential as a biomarker or therapeutic target in various clinical contexts are welcome.

Dr. Félix A. Ruiz
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • polyphosphate
  • polyP
  • biomarker and therapeutic target

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Published Papers (3 papers)

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Research

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12 pages, 1751 KB  
Article
Platelet Polyphosphate Signals Through NFκB to Induce Myofibroblast Differentiation
by Patrick M. Suess, Chanel C. La, Sreeparna Vappala, Jayachandran N. Kizhakkedathu and James H. Morrissey
Biomolecules 2025, 15(10), 1441; https://doi.org/10.3390/biom15101441 - 12 Oct 2025
Viewed by 630
Abstract
Myofibroblasts drive wound healing and fibrotic disease through generation of contractile force to promote wound closure and production of matrix proteins to generate scar tissue. Platelets secrete many pro-wound healing molecules, including cytokines and growth factors. We previously reported that inorganic polyphosphate, secreted [...] Read more.
Myofibroblasts drive wound healing and fibrotic disease through generation of contractile force to promote wound closure and production of matrix proteins to generate scar tissue. Platelets secrete many pro-wound healing molecules, including cytokines and growth factors. We previously reported that inorganic polyphosphate, secreted by activated platelets, is chemotactic for fibroblasts and induces a myofibroblast phenotype. Using NIH-3T3 cells and primary human fibroblasts, we examined the impact of inhibitors of cell-surface receptors and intracellular signaling molecules on polyphosphate-induced myofibroblast differentiation. We now report that polyphosphate-induced differentiation of fibroblasts to myofibroblasts occurs through a signaling pathway mediated by the receptor for advanced glycation end products (RAGE) and nuclear factor kappa B (NFκB) transcription factor. Inhibition of these signaling components ablated the effects of polyphosphate on fibroblasts. Platelet releasates also induced NFκB signaling and myofibroblast differentiation. Blocking the polyphosphate content of platelet releasates with a biocompatible polyP inhibitor rendered the releasates unable to induce myofibroblast differentiation. These results identify a cell-surface receptor and intracellular transcription factor utilized by platelet polyphosphate to promote wound healing through myofibroblast differentiation and may provide targets for promoting wound healing or altering the disease progression of fibrosis. Full article
(This article belongs to the Special Issue Polyphosphate (PolyP) in Health and Disease)
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22 pages, 4024 KB  
Article
Inorganic Polyphosphate Modulates Chromosome Transmission Fidelity in the Fission Yeast Schizosaccharomyces pombe
by Sarune Bollé, Elisa Koc, Adolfo Saiardi, Lisa Juhran, Eva Walla, Ursula Fleig and Abel Alcázar-Román
Biomolecules 2025, 15(9), 1331; https://doi.org/10.3390/biom15091331 - 18 Sep 2025
Viewed by 902
Abstract
Chromosome transmission fidelity is vital for organism fitness. Yet, extrinsic and intrinsic changes can affect this process, leading to aneuploidy, the loss/gain of chromosomes, which is a hallmark of cancer. Here, using a haploid fission yeast Schizosaccharomyces pombe strain with a segmental aneuploidy, [...] Read more.
Chromosome transmission fidelity is vital for organism fitness. Yet, extrinsic and intrinsic changes can affect this process, leading to aneuploidy, the loss/gain of chromosomes, which is a hallmark of cancer. Here, using a haploid fission yeast Schizosaccharomyces pombe strain with a segmental aneuploidy, we assayed genome stability under different temperatures and altered gene dosage. We find that S. pombe genome stability is temperature-dependent and is unexpectedly modulated by intracellular levels of inorganic polyphosphate polymers (polyP). The vtc4+ gene, encoding a subunit of the polyP-generating VTC complex, is present twice due to the segmental aneuploidy resulting in a gene-dosage-coupled increase in polyP. Using strains with different amounts of polyP, we find a direct negative correlation between polyP and chromosome segregation fidelity. PolyP modulates the function of the conserved CCAN kinetochore subcomplex, as the abnormal growth phenotype caused by the mutant CCAN protein Fta2-291 was rescued in the absence of polyP, while extra polyP had the opposite effect. Importantly, this appears to occur in part by modulation of the nucleolin Gar2. Gar2 is the functional homolog of the Saccharomyces cerevisiae Nsr1 protein, whose function is modulated by posttranslational polyP-mediated polyphosphorylation. Thus, polyP modulates genome stability, linking cellular metabolism to chromosome transmission fidelity. Full article
(This article belongs to the Special Issue Polyphosphate (PolyP) in Health and Disease)
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Review

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29 pages, 1763 KB  
Review
Inorganic Polyphosphate: An Emerging Regulator of Neuronal Bioenergetics and Its Implications in Neuroprotection
by Marcela Montilla, Norma Pavas-Escobar, Iveth Melissa Guatibonza-Arévalo, Alejandro Múnera, Renshen Eduardo Rivera-Melo and Felix A. Ruiz
Biomolecules 2025, 15(8), 1060; https://doi.org/10.3390/biom15081060 - 22 Jul 2025
Viewed by 1366
Abstract
Inorganic polyphosphate (polyP) is an evolutionarily conserved polymer that has recently gained relevance in neuronal physiology and pathophysiology. Although its roles, such as mitochondrial bioenergetics, calcium homeostasis, and the oxidative stress response, for example, are increasingly recognized, its specific implications in neurological disorders [...] Read more.
Inorganic polyphosphate (polyP) is an evolutionarily conserved polymer that has recently gained relevance in neuronal physiology and pathophysiology. Although its roles, such as mitochondrial bioenergetics, calcium homeostasis, and the oxidative stress response, for example, are increasingly recognized, its specific implications in neurological disorders remain underexplored. This review focuses on synthesizing the current knowledge of polyP in the context of central nervous system (CNS) diseases, highlighting how its involvement in key mitochondrial processes may influence neuronal survival and function. In particular, we examine recent evidence linking polyP to mechanisms relevant to neurodegeneration, such as the modulation of the mitochondrial permeability transition pore (mPTP), regulation of amyloid fibril formation, and oxidative stress responses. In addition, we analyze the emerging roles of polyP in inflammation and related cell signaling in CNS disorders. By organizing the existing data around the potential pathological and protective roles of polyP in the CNS, this review identifies it as a candidate of interest in the context of neurodegenerative disease mechanisms. We aim to clarify its relevance and stimulate future research on its molecular mechanisms and translational potential. Full article
(This article belongs to the Special Issue Polyphosphate (PolyP) in Health and Disease)
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