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. 2020 Jun:15:104-110.
doi: 10.1016/j.cophys.2019.12.011. Epub 2019 Dec 31.

Sleep and Cellular Stress

Julie A Williams  1   2 , Nirinjini Naidoo  2   3
Affiliations

Sleep and Cellular Stress

Julie A Williams et al. Curr Opin Physiol. 2020 Jun.

Abstract

Sleep is a universal phenomenon occurring in all species studied thus far. Sleep loss results in adverse physiological effects at both the organismal and cellular levels suggesting an adaptive role for sleep in the maintenance of overall health. This review examines the bidirectional relationship between sleep and cellular stress. Cellular stress in this review refers to a shift in cellular homeostasis in response to an external stressor. Studies that illustrate the fact that sleep loss induces cellular stress and those that provide evidence that cellular stress in turn promotes sleep will be discussed.

Keywords: DNA repair; ER stress; Epidermal Growth Factor; NFκB; Unfolded protein response; immune; inflammation.

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Conflict of interest statement

Conflict of Interest Statement The authors declare no conflict of interest

Figures

Figure 1:
Figure 1:
Schematic illustrating the relationship between sleep and cellular stress responses
Figure 2:
Figure 2:
Simplified scheme showing the adaptive, inflammatory and apoptotic phases of the UPR. The three ER stress sensors (PERK, IRE1 and ATF6) are activated upon dissociation from BiP initiating signaling events that increase protein-folding capacity and reduce protein load on the ER. Phosphorylation of eukaryotic Initiation Factor 2α (eIF2α) by PERK inhibits protein translation, while IRE1 activation leads to splicing of xbp1 and chaperone production as well as regulated IRE1-dependent decay (RIDD). Both ATF6 and IRE1 contribute to ER associated degradation (ERAD) of misfolded proteins. These transcriptional and translational outputs tend to re-establish protein-folding homeostasis in the ER and promote cell survival. JNK activation downstream of IRE1 contributes to inflammatory signaling. Activated IRE1 acting on downstream factors activates JNK and caspases. ATF4 dependent transcription in mammals leads to increases in C/ebp homologous binding protein (CHOP), a pro-apoptotic transcription factor. CHOP and JNK also promote the translocation of Bax (BCl-2 associated X protein) to the mitochondria where it facilitates the release of cytochrome c required for caspase activation. ER specific caspases are thought to directly induce cell death. Translation attenuation leads to NFκB entry into the nucleus and transcription of inflammatory genes. Calcium release from the ER, exacerbated protein synthesis, and ROS production influences the induction of apoptosis.
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