daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival.

Journal Article (Journal Article)

daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant.

Full Text

Duke Authors

Cited Authors

  • Hibshman, JD; Doan, AE; Moore, BT; Kaplan, RE; Hung, A; Webster, AK; Bhatt, DP; Chitrakar, R; Hirschey, MD; Baugh, LR

Published Date

  • October 24, 2017

Published In

Volume / Issue

  • 6 /

PubMed ID

  • 29063832

Pubmed Central ID

  • PMC5655125

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.30057


  • eng

Conference Location

  • England