Endogenous NHR ligands: metabolomics to the rescue.

Axel Bethke,Frank C Schroeder

doi:10.18632/aging.100676

Abstract

Endogenous NHR ligands: metabolomics to the rescue.

Highlights

Whereas storage of information in biological systems generally relies on large macromolecules, e.g. DNA and RNA, signaling, that is transduction of information, proceeds to a large extent via biogenic small molecules, metabolites of diverse chemical make-up and biosynthetic history
The last step in DAF-12 ligand biosynthesis is catalyzed by a cytochrome p450 called DAF-9, which converts inactive precursor steroids into the active ligands that bind to DAF-12, thereby promoting reproductive development (Gerisch et al, Dev Cell; 2001)
Following pioneering work by Antebi and others, Motola et al used a bold candidate-based approach combined with an array of in-vivo and in-vitro assays to show that two cholestenoic acid derivatives, named Δ4and Δ7-dafachronic acid (DA), activate DAF-12 and promote reproductive development in C. elegans (Motola et al, Cell; 2006)

Summary

Introduction

Whereas storage of information in biological systems generally relies on large macromolecules, e.g. DNA and RNA, signaling, that is transduction of information, proceeds to a large extent via biogenic small molecules, metabolites of diverse chemical make-up and biosynthetic history. In the absence of its endogenous steroidal ligands DAF-12 promotes arrest of larval development and entry into a long-lived, highly stress-resistant alternate larval stage called dauer, whereas liganded DAF-12 allows rapid maturation of larvae to reproductive adults (Antebi et al, Genes Dev; 2000, Lee and Schroeder, PLoS Biol; 2012).

Results

Conclusion