Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response
Author
Samper Martín, Bàrbara
Sarrias, Ana
Lázaro, Blanca
Pérez-Montero, Marta
Rodríguez-Rodríguez, Rosalía
P.C. Ribeiro, Mariana
Bañón, Aitor
Wolfgeher, Donald
Jessen, Henning J.
Alsina, Berta
Clotet Erra, Josep
Kron, Stephen J.
Saiardi, Adolfo
Jiménez, Javier
Bru Rullo, Samuel
Publication date
2021ISSN
2211-1247
Abstract
Polyphosphate (polyP) is a polymer of hundreds of phosphate residues present in all organisms. In mammals, polyP is involved in crucial physiological processes, including coagulation, inflammation, and stress response. However, after decades of research, the metabolic enzymes are still unknown. Here, we purify and identify Nudt3, a NUDIX family member, as the enzyme responsible for polyP phosphatase activity in mammalian cells. We show that Nudt3 shifts its substrate specificity depending on the cation; specifically, Nudt3 is active on polyP when Zn2+ is present. Nudt3 has in vivo polyP phosphatase activity in human cells, and importantly, we show that cells with altered polyP levels by modifying Nudt3 protein amount present reduced viability upon oxidative stress and increased DNA damage, suggesting that polyP and Nudt3 play a role in oxidative stress protection. Finally, we show that Nudt3 is involved in the early stages of embryo development in zebrafish.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
57 - Biological sciences in general
61 - Medical sciences
Keywords
Polifosfat
Polifosfats de mamífers
Dany a l'ADN
Estrès oxidatiu
Polifosfato
Polifosfatos de mamíferos
Daño en el ADN
Estrés oxidativo
Polyphosphate
Mammalian polyphosphates
DNA damage
Oxidative stress
Pages
19
Publisher
Elsevier
Collection
37;7
Is part of
Cell Reports
Citation
Samper-Martín, Bàrbara; Sarrias, Ana; Lázaro, Blanca [et al.]. Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response. Cell Reports, 2021, 37(7), 110004. Disponible en: <https://www.sciencedirect.com/science/article/pii/S2211124721014820#bib30>. Fecha de acceso: 10 dic. 2021. DOI: 10.1016/j.celrep.2021.110004.
This item appears in the following Collection(s)
- Ciències de la Salut [725]
Rights
Under a Creative Commons license
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/