title: Increased levels of hydrogen peroxide induce a HIF-1-dependent modification of lipid metabolism in AMPK compromised C. elegans dauer larvae.
abstract: Cells have evolved numerous mechanisms to circumvent stresses caused by the environment, and many of them are regulated by the AMP-activated kinase (AMPK). Unlike most organisms, C. elegans AMPK-null mutants are viable, but they die prematurely in the "long-lived" dauer stage due to exhaustion of triglyceride stores. Using a genome-wide RNAi approach, we demonstrate that the disruption of genes that increase hydrogen peroxide levels enhance the survival of AMPK mutant dauers by altering both the abundance and the nature of the fatty-acid content in the animal by increasing the HIF-1-dependent expression of several key enzymes involved in fatty-acid biosynthesis. Our data provide a mechanistic foundation to explain how an optimal level of an often vilified ROS-generating compound such as hydrogen peroxide can provide cellular benefit, a phenomenon described as hormesis, by instructing cells to readjust their lipid biosynthetic capacity through downstream HIF-1 activation to correct cellular energy deficiencies.
authors.affiliation: Developmental Biology Research Initiative, Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montreal, QC H3A 1B1, Canada.
authors.forename: Meng
authors.initials: M
authors.lastname: Xie
authors.forename: Richard
authors.initials: R
authors.lastname: Roy
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000704:Analysis of Variance; D000818:Animals; D001391:Azo Compounds; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007814:Larva / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000502:physiology; D009154:Mutation / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001391:Azo Compounds; D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; C541178:HIF-1 protein, C elegans; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D002374:Catalase; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; C011049:oil red O