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Hypoxia disrupts proteostasis in Caenorhabditis elegans
Author(s) -
Fawcett Emily M.,
Hoyt Jill M.,
Johnson Jenna K.,
Miller Dana L.
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12301
Subject(s) - proteostasis , biology , hypoxia (environmental) , microbiology and biotechnology , caenorhabditis elegans , transcription factor , biochemistry , gene , oxygen , chemistry , organic chemistry
Summary Oxygen is fundamentally important for cell metabolism, and as a consequence, O 2 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 (H 2 S) protects animals from hypoxia‐induced disruption of proteostasis. H 2 S has been shown to protect against hypoxic damage in mammals and extends lifespan in nematodes. Remarkably, our data also show that H 2 S can reverse detrimental effects of hypoxia on proteostasis. Our data indicate that the protective effects of H 2 S in hypoxia are mechanistically distinct from the effect of H 2 S 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.

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