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Mechanisms underlying hypoxia tolerance in drosophila melanogaster: Hairy as a metabolic switch

Academic Article
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Overview

authors

  • Zhou, D.
  • Xue, J.
  • Lai, J. C. K.
  • Schork, Nicholas
  • White, K. P.
  • Haddad, G. G.

publication date

  • October 2008

journal

  • PLoS Genetics  Journal

abstract

  • Hypoxia-induced cell injury has been related to multiple pathological conditions. In order to render hypoxia-sensitive cells and tissues resistant to low O2 environment, in this current study, we used Drosophila melanogaster as a model to dissect the mechanisms underlying hypoxia-tolerance. A D. melanogaster strain that lives perpetually in an extremely low-oxygen environment (4% O2, an oxygen level that is equivalent to that over about 4,000 m above Mt. Everest) was generated through laboratory selection pressure using a continuing reduction of O2 over many generations. This phenotype is genetically stable since selected flies, after several generations in room air, survive at this low O2 level. Gene expression profiling showed striking differences between tolerant and naïve flies, in larvae and adults, both quantitatively and qualitatively. Up-regulated genes in the tolerant flies included signal transduction pathways (e.g., Notch and Toll/Imd pathways), but metabolic genes were remarkably down-regulated in the larvae. Furthermore, a different allelic frequency and enzymatic activity of the triose phosphate isomerase (TPI) was present in the tolerant versus naïve flies. The transcriptional suppressor, hairy, was up-regulated in the microarrays and its binding elements were present in the regulatory region of the specifically down-regulated metabolic genes but not others, and mutations in hairy significantly reduced hypoxia tolerance. We conclude that, the hypoxia-selected flies: (a) altered their gene expression and genetic code, and (b) coordinated their metabolic suppression, especially during development, with hairy acting as a metabolic switch, thus playing a crucial role in hypoxia-tolerance.

subject areas

  • Altitude
  • Animals
  • Anoxia
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Citric Acid Cycle
  • DNA
  • Disease Models, Animal
  • Drosophila Proteins
  • Drosophila melanogaster
  • Electron Transport
  • Gene Expression
  • Gene Expression Profiling
  • Genes, Insect
  • Glycolysis
  • Larva
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Repressor Proteins
  • Sequence Homology, Nucleic Acid
  • Signal Transduction
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Identity

PubMed Central ID

  • PMC2556400

International Standard Serial Number (ISSN)

  • 1553-7390

Digital Object Identifier (DOI)

  • 10.1371/journal.pgen.1000221

PubMed ID

  • 18927626
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Additional Document Info

start page

  • e1000221

volume

  • 4

issue

  • 10

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