Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress.

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 progres

SUBMITTER: Jobava R 

PROVIDER: S-EPMC8559772 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature