Tolerance to Hypoxia Is Promoted by FOXO Regulation of the Innate Immunity Transcription Factor NF-κB/Relish in Drosophila

We find that upon hypoxia exposure, Forkhead Box-O transcriptional activity is rapidly induced in both larvae and adults

Elizabeth C Barretto; Danielle M Polan; Amy N Beevor-Potts; Byoungchun Lee; Savraj S Grewal

2020

Scholarcy highlights

  • Exposure of tissues and organs to low oxygen occurs in both physiological and pathological conditions in animals
  • We report that Forkhead Box-O is a hypoxia-inducible factor required for organismal survival in low oxygen, and we show that one way that FOXO functions is through upregulation of Relish/NF-kB
  • Together with previous studies in C. elegans and Zebrafish showing that reduced insulin signaling and FOXO induction confer hypoxia tolerance, our work suggests that FOXO is a conserved mediator of hypoxia responses
  • We found that the induction of FOXO upon hypoxia occurs in sima mutants, suggesting that the FOXO hypoxic response occurs independently of the classically described HIF-1a response
  • In vivo genetic studies in model organisms suggest that the HIF-1a and FOXO transcription factors may act in parallel to mediate responses to hypoxia
  • In C. elegans, the extension of life span caused by hypoxia and increased HIF-1a protein levels occurs in the absence of FOXO nuclear localization and function
  • These data, together with previous work showing hypoxia induction of Relish, suggest that induction of an immune-like transcriptional response may be a protective mechanism in low oxygen in Drosophila

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