Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response
Summary: 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 unkn...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721014820 |
| _version_ | 1819000182156558336 |
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| author | Bàrbara Samper-Martín Ana Sarrias Blanca Lázaro Marta Pérez-Montero Rosalía Rodríguez-Rodríguez Mariana P.C. Ribeiro Aitor Bañón Don Wolfgeher Henning J. Jessen Berta Alsina Josep Clotet Stephen J. Kron Adolfo Saiardi Javier Jiménez Samuel Bru |
| author_facet | Bàrbara Samper-Martín Ana Sarrias Blanca Lázaro Marta Pérez-Montero Rosalía Rodríguez-Rodríguez Mariana P.C. Ribeiro Aitor Bañón Don Wolfgeher Henning J. Jessen Berta Alsina Josep Clotet Stephen J. Kron Adolfo Saiardi Javier Jiménez Samuel Bru |
| author_sort | Bàrbara Samper-Martín |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-20T22:29:15Z |
| format | Article |
| id | doaj.art-90c4e621b4e446d2a23899e2baa3a8aa |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T22:29:15Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-90c4e621b4e446d2a23899e2baa3a8aa2022-12-21T19:24:46ZengElsevierCell Reports2211-12472021-11-01377110004Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress responseBàrbara Samper-Martín0Ana Sarrias1Blanca Lázaro2Marta Pérez-Montero3Rosalía Rodríguez-Rodríguez4Mariana P.C. Ribeiro5Aitor Bañón6Don Wolfgeher7Henning J. Jessen8Berta Alsina9Josep Clotet10Stephen J. Kron11Adolfo Saiardi12Javier Jiménez13Samuel Bru14Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, SpainFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, SpainFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, SpainFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, SpainFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, SpainFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, SpainDepartment of Experimental and Health Sciences, Universitat Pompeu Fabra-Parc de Recerca Biomèdica, 08003 Barcelona, SpainDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USAInstitute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany; CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, GermanyDepartment of Experimental and Health Sciences, Universitat Pompeu Fabra-Parc de Recerca Biomèdica, 08003 Barcelona, SpainFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, SpainDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USAMedical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E6BT, UKFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, Spain; Corresponding authorFaculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Barcelona, Spain; Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721014820polyphosphateNudt3NUDIXmammalian polyphosphataseoxidative stressDNA damage |
| spellingShingle | Bàrbara Samper-Martín Ana Sarrias Blanca Lázaro Marta Pérez-Montero Rosalía Rodríguez-Rodríguez Mariana P.C. Ribeiro Aitor Bañón Don Wolfgeher Henning J. Jessen Berta Alsina Josep Clotet Stephen J. Kron Adolfo Saiardi Javier Jiménez Samuel Bru Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response Cell Reports polyphosphate Nudt3 NUDIX mammalian polyphosphatase oxidative stress DNA damage |
| title | Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response |
| title_full | Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response |
| title_fullStr | Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response |
| title_full_unstemmed | Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response |
| title_short | Polyphosphate degradation by Nudt3-Zn2+ mediates oxidative stress response |
| title_sort | polyphosphate degradation by nudt3 zn2 mediates oxidative stress response |
| topic | polyphosphate Nudt3 NUDIX mammalian polyphosphatase oxidative stress DNA damage |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721014820 |
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