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Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans

Metabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the role...

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Autores principales: Possik, Elite, Schmitt, Clémence, Al-Mass, Anfal, Bai, Ying, Côté, Laurence, Morin, Johanne, Erb, Heidi, Oppong, Abel, Kahloan, Wahab, Parker, J. Alex, Madiraju, S. R. Murthy, Prentki, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752807/
https://www.ncbi.nlm.nih.gov/pubmed/35017476
http://dx.doi.org/10.1038/s41467-021-27803-6
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author Possik, Elite
Schmitt, Clémence
Al-Mass, Anfal
Bai, Ying
Côté, Laurence
Morin, Johanne
Erb, Heidi
Oppong, Abel
Kahloan, Wahab
Parker, J. Alex
Madiraju, S. R. Murthy
Prentki, Marc
author_facet Possik, Elite
Schmitt, Clémence
Al-Mass, Anfal
Bai, Ying
Côté, Laurence
Morin, Johanne
Erb, Heidi
Oppong, Abel
Kahloan, Wahab
Parker, J. Alex
Madiraju, S. R. Murthy
Prentki, Marc
author_sort Possik, Elite
collection PubMed
description Metabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the roles of a recently discovered enzyme at the heart of metabolism in mammalian cells, glycerol-3-phosphate phosphatase (G3PP) (gene name Pgp) that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol. We identify three Pgp homologues in C. elegans (pgph) and demonstrate in vivo that their protein products have G3PP activity, essential for glycerol synthesis. We demonstrate that PGPH/G3PP regulates the adaptation to various stresses, in particular hyperosmolarity and glucotoxicity. Enhanced G3PP activity reduces fat accumulation, promotes healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility. Thus, PGP/G3PP can be considered as a target for age-related metabolic disorders.
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spelling pubmed-87528072022-01-20 Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans Possik, Elite Schmitt, Clémence Al-Mass, Anfal Bai, Ying Côté, Laurence Morin, Johanne Erb, Heidi Oppong, Abel Kahloan, Wahab Parker, J. Alex Madiraju, S. R. Murthy Prentki, Marc Nat Commun Article Metabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the roles of a recently discovered enzyme at the heart of metabolism in mammalian cells, glycerol-3-phosphate phosphatase (G3PP) (gene name Pgp) that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol. We identify three Pgp homologues in C. elegans (pgph) and demonstrate in vivo that their protein products have G3PP activity, essential for glycerol synthesis. We demonstrate that PGPH/G3PP regulates the adaptation to various stresses, in particular hyperosmolarity and glucotoxicity. Enhanced G3PP activity reduces fat accumulation, promotes healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility. Thus, PGP/G3PP can be considered as a target for age-related metabolic disorders. Nature Publishing Group UK 2022-01-11 /pmc/articles/PMC8752807/ /pubmed/35017476 http://dx.doi.org/10.1038/s41467-021-27803-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Possik, Elite
Schmitt, Clémence
Al-Mass, Anfal
Bai, Ying
Côté, Laurence
Morin, Johanne
Erb, Heidi
Oppong, Abel
Kahloan, Wahab
Parker, J. Alex
Madiraju, S. R. Murthy
Prentki, Marc
Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
title Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
title_full Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
title_fullStr Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
title_full_unstemmed Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
title_short Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans
title_sort phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in c. elegans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752807/
https://www.ncbi.nlm.nih.gov/pubmed/35017476
http://dx.doi.org/10.1038/s41467-021-27803-6
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