Jobava, Raul, Mao, Yuanhui, Guan, Bo-Jhih, Hu, Di ORCID: 0000-0003-4047-7340, Krokowski, Dawid, Chen, Chien-Wen ORCID: 0000-0002-1214-4058, Shu, Xin Erica, Chukwurah, Evelyn ORCID: 0000-0002-9706-7003, Wu, Jing, Gao, Zhaofeng, Zagore, Leah L., Merrick, William C., Trifunovic, Aleksandra, Hsieh, Andrew C., Valadkhan, Saba, Zhang, Youwei, Qi, Xin ORCID: 0000-0002-9578-3890, Jankowsky, Eckhard, Topisirovic, Ivan, Licatalosi, Donny D., Qian, Shu-Bing and Hatzoglou, Maria (2021). Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress. Mol. Cell, 81 (20). S. 4191 - 4218. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jobava, RaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mao, YuanhuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guan, Bo-JhihUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, DiUNSPECIFIEDorcid.org/0000-0003-4047-7340UNSPECIFIED
Krokowski, DawidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, Chien-WenUNSPECIFIEDorcid.org/0000-0002-1214-4058UNSPECIFIED
Shu, Xin EricaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chukwurah, EvelynUNSPECIFIEDorcid.org/0000-0002-9706-7003UNSPECIFIED
Wu, JingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, ZhaofengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zagore, Leah L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merrick, William C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hsieh, Andrew C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valadkhan, SabaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, YouweiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qi, XinUNSPECIFIEDorcid.org/0000-0002-9578-3890UNSPECIFIED
Jankowsky, EckhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Topisirovic, IvanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Licatalosi, Donny D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qian, Shu-BingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hatzoglou, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-595185
DOI: 10.1016/j.molcel.2021.09.029
Journal or Publication Title: Mol. Cell
Volume: 81
Number: 20
Page Range: S. 4191 - 4218
Date: 2021
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4164
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
UNFOLDED PROTEIN RESPONSE; IN-VIVO; GENE-EXPRESSION; INITIATION; PROMOTES; CELLS; SUPPRESSION; HIBERNATION; INHIBITION; DEPHOSPHORYLATIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59518

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