Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response

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...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:20.500.12328/3003
Acceso en línea:http://hdl.handle.net/20.500.12328/3003
https://dx.doi.org/10.1016/j.celrep.2021.110004
Access Level:acceso abierto
Palabra clave: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
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Descripción
Sumario: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.

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