Open AccessProlonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression
Author(s) -
Somayeh Pourpirali,
Cristina Valacca,
Paola Merlo,
Salvatore Rizza,
Silvia D’Amico,
Francesco Cecconi
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0129750
Subject(s) - autophagy , microbiology and biotechnology , messenger rna , apoptosis , cytoplasm , programmed cell death , chemistry , biology , gene , biochemistry
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 (CoCl 2 ). We observed that, upon CoCl 2 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 re-localization of Ambra1 mRNA to non-translating fractions and cytoplasmic P-bodies was further detected. Thus, in this pseudohypoxic context, Ambra1 mRNA translocation to P-bodies and translational suppression correlated with increased cell death.