Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress.
Mol Cell
; 81(20): 4191-4208.e8, 2021 10 21.
Article
em En
| MEDLINE
| ID: mdl-34686314
ABSTRACT
To survive, mammalian cells must adapt to environmental challenges. While the cellular response to mild stress has been widely studied, how cells respond to severe stress remains unclear. We show here that under severe hyperosmotic stress, cells enter a transient hibernation-like state in anticipation of recovery. We demonstrate this adaptive pausing response (APR) is a coordinated cellular response that limits ATP supply and consumption through mitochondrial fragmentation and widespread pausing of mRNA translation. This pausing is accomplished by ribosome stalling at translation initiation codons, which keeps mRNAs poised to resume translation upon recovery. We further show that recovery from severe stress involves ISR (integrated stress response) signaling that permits cell cycle progression, resumption of growth, and reversal of mitochondria fragmentation. Our findings indicate that cells can respond to severe stress via a hibernation-like mechanism that preserves vital elements of cellular function under harsh environmental conditions.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pressão Osmótica
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Ribossomos
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Biossíntese de Proteínas
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Proteínas Mitocondriais
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Proliferação de Células
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Fibroblastos
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Mitocôndrias
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article