Hypoxia disrupts proteostasis in Caenorhabditis elegans
| Autor: | Jill M. Hoyt, Jenna K. Johnson, Dana L. Miller, Emily M. Fawcett |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Aging
Biology Protein aggregation Protein Aggregation Pathological protein aggregation 03 medical and health sciences Protein Aggregates 0302 clinical medicine medicine Protein biosynthesis Animals Homeostasis Paralysis Hydrogen Sulfide Caenorhabditis elegans Caenorhabditis elegans Proteins Transcription factor 030304 developmental biology 0303 health sciences proteostasis hypoxia H2S Cell Biology Original Articles Hypoxia (medical) biology.organism_classification C. elegans Adaptation Physiological Cell Hypoxia Cell biology Disease Models Animal Proteostasis Cell metabolism Nerve Degeneration medicine.symptom Peptides oxygen Polyglutamine 030217 neurology & neurosurgery |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 1474-9718 |
| Popis: | Oxygen is fundamentally important for cell metabolism, and as a consequence, O2 deprivation (hypoxia) can impair many essential physiological processes. Here, we show that an active response to hypoxia disrupts cellular proteostasis – the coordination of protein synthesis, quality control, and degradation that maintains the functionality of the proteome. We have discovered that specific hypoxic conditions enhance the aggregation and toxicity of aggregation-prone proteins that are associated with neurodegenerative diseases. Our data indicate this is an active response to hypoxia, rather than a passive consequence of energy limitation. This response to hypoxia is partially antagonized by the conserved hypoxia-inducible transcription factor, hif-1. We further demonstrate that exposure to hydrogen sulfide (H2S) protects animals from hypoxia-induced disruption of proteostasis. H2S has been shown to protect against hypoxic damage in mammals and extends lifespan in nematodes. Remarkably, our data also show that H2S can reverse detrimental effects of hypoxia on proteostasis. Our data indicate that the protective effects of H2S in hypoxia are mechanistically distinct from the effect of H2S to increase lifespan and thermotolerance, suggesting that control of proteostasis and aging can be dissociated. Together, our studies reveal a novel effect of the hypoxia response in animals and provide a foundation to understand how the integrated proteostasis network is integrated with this stress response pathway. |
| Databáze: | OpenAIRE |
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