Prolonged pseudohypoxia targets Ambra1 mRNA to P-bodies for translational repression

Somayeh Pourpirali, Cristina Valacca, Paola Merlo, Salvatore Rizza, Silvia D'Amico, Francesco Cecconi

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia has been associated with several pathological conditions ranging from stroke to cancer. This condition results in the activation of autophagy, a cyto-protective response involving the formation of double-membraned structures, the autophagosomes, in the cytoplasm. In this study, we investigated the cellular mechanisms regulating the autophagy gene Ambra1, after exposure to a hypoxia mimetic, cobalt chloride (CoCl2). We observed that, upon CoCl2 administration, activation of the apoptotic machinery was concomitant with down-regulation of the pro-autophagic factor Ambra1, without affecting transcription. Additionally, co-treating the cells with the caspase inhibitor z-VAD-FMK did not restore Ambra1 protein levels, this implying the involvement of other regulatory mechanisms. Partial relocalization of Ambra1 mRNA to non-translating fractions and cytoplasmic P-bodies was further detected. Thus, in this pseudohypoxic context, Ambra1 mRNA translocation to Pbodies and translational suppression correlated with increased cell death.

Original languageEnglish
Article numbere0129750
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 18 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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