RRC ID 76033
Author Possik E, Schmitt C, Al-Mass A, Bai Y, Côté L, Morin J, Erb H, Oppong A, Kahloan W, Parker JA, Madiraju SRM, Prentki M.
Title Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans.
Journal Nat Commun
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.
Volume 13(1)
Pages 177
Published 2022-1-11
DOI 10.1038/s41467-021-27803-6
PII 10.1038/s41467-021-27803-6
PMID 35017476
PMC PMC8752807
MeSH Adaptation, Physiological / genetics* Amino Acid Sequence Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caloric Restriction Eating / genetics Gene Expression Regulation Glucose / metabolism Glucose / pharmacology Glycerol / metabolism Glycerol-3-Phosphate O-Acyltransferase / genetics Glycerol-3-Phosphate O-Acyltransferase / metabolism Glycerophosphates / metabolism* Helminth Proteins / genetics* Helminth Proteins / metabolism Isoenzymes / genetics Isoenzymes / metabolism Longevity / genetics* Osmolar Concentration Phosphoric Monoester Hydrolases / genetics* Phosphoric Monoester Hydrolases / metabolism Sequence Alignment Sequence Homology, Amino Acid Stearoyl-CoA Desaturase / genetics Stearoyl-CoA Desaturase / metabolism Stress, Physiological / genetics
C.elegans tm3391