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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2015 (arch)     Display Documents

ID: 717946.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2015 (arch)
Integration of carbohydrate metabolism and redox state controls dauer larva formation in Caenorhabditis elegans.
Authors:Penkov, Sider; Kaptan, Damla; Erkut, Cihan; Sarov, Mihail; Mende, Fanny; Kurzchalia, Teymuras V.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Nature Communications
Sequence Number of Article:8060
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Under adverse conditions, Caenorhabditis elegans enters a diapause stage called the dauer larva. External cues signal the nuclear hormone receptor DAF-12, the activity of which is regulated by its ligands: dafachronic acids (DAs). DAs are synthesized from cholesterol, with the last synthesis step requiring NADPH, and their absence stimulates dauer formation. Here we show that NADPH levels determine dauer formation in a regulatory mechanism involving key carbohydrate and redox metabolic enzymes. Elevated trehalose biosynthesis diverts glucose-6-phosphate from the pentose phosphate pathway, which is the major source of cellular NADPH. This enhances dauer formation due to the decrease in the DA level. Moreover, DAF-12, in cooperation with DAF-16/FoxO, induces negative feedback of DA synthesis via activation of the trehalose-producing enzymes TPS-1/2 and inhibition of the NADPH-producing enzyme IDH-1. Thus, the dauer developmental decision is controlled by integration of the metabolic flux of carbohydrates and cellular redox potential.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
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