Phosphoglycolate Phosphatase Homologs Act As Glycerol-3-phosphate Phosphatase to Control Stress and Healthspan in C. Elegans

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jan 12

PMID 35017476

Authors

Elite Possik

Clemence Schmitt

Anfal Al-Mass

Ying Bai

Laurence Cote

Johanne Morin

Heidi Erb

Abel Oppong

Wahab Kahloan

J Alex Parker

S R Murthy Madiraju

Marc Prentki

Affiliations

Soon will be listed here.

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.

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