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

Elite Possik, Clémence Schmitt, Anfal Al-Mass, Ying Bai, Laurence Côté, Johanne Morin, Heidi Erb, Abel Oppong, Wahab Kahloan, J. Alex Parker, S. R. Murthy Madiraju () and Marc Prentki ()
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Elite Possik: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Clémence Schmitt: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Anfal Al-Mass: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Ying Bai: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Laurence Côté: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Johanne Morin: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Heidi Erb: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Abel Oppong: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Wahab Kahloan: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
J. Alex Parker: Department of Neurosciences, CRCHUM
S. R. Murthy Madiraju: Université de Montréal, Montreal Diabetes Research Center, CRCHUM
Marc Prentki: Université de Montréal, Montreal Diabetes Research Center, CRCHUM

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27803-6

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DOI: 10.1038/s41467-021-27803-6

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