TY - JOUR
T1 - Prolonged pseudohypoxia targets Ambra1 mRNA to P-bodies for translational repression
AU - Pourpirali, Somayeh
AU - Valacca, Cristina
AU - Merlo, Paola
AU - Rizza, Salvatore
AU - D'Amico, Silvia
AU - Cecconi, Francesco
PY - 2015/6/18
Y1 - 2015/6/18
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0129750
DO - 10.1371/journal.pone.0129750
M3 - Article
AN - SCOPUS:84939180183
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e0129750
ER -