Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression.
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 investigat...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0129750 |
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| Summary: | 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 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. |
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| ISSN: | 1932-6203 |