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Cell Death Dis. 2018 Nov 13;9(11):1129. doi: 10.1038/s41419-018-1173-x.

Nitric oxide triggers the assembly of "type II" stress granules linked to decreased cell viability.

Aulas A1,2, Lyons SM1,2, Fay MM1,2, Anderson P3,4, Ivanov P5,6,7.

Author information

1
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, 02115, USA.
2
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
3
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, 02115, USA. panderson@rics.bwh.harvard.edu.
4
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. panderson@rics.bwh.harvard.edu.
5
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, 02115, USA. pivanov@rics.bwh.harvard.edu.
6
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. pivanov@rics.bwh.harvard.edu.
7
The Broad Institute of Harvard and M.I.T., Cambridge, MA, 02142, USA. pivanov@rics.bwh.harvard.edu.

Abstract

We show that 3-morpholinosydnonimine (SIN-1)-induced nitric oxide (NO) triggers the formation of SGs. Whereas the composition of NO-induced SGs is initially similar to sodium arsenite (SA)-induced type I (cytoprotective) SGs, the progressive loss of eIF3 over time converts them into pro-death (type II) SGs. NO-induced SG assembly requires the phosphorylation of eIF2α, but the transition to type II SGs is temporally linked to the mTOR-regulated displacement of eIF4F complexes from the m7 guanine cap. Whereas SA does not affect mitochondrial morphology or function, NO alters mitochondrial integrity and function, resulting in increased ROS production, decreased cytoplasmic ATP, and plasma membrane permeabilization, all of which are supported by type II SG assembly. Thus, cellular energy balance is linked to the composition and function of NO-induced SGs in ways that determine whether cells live or die.

PMID:
30425239
PMCID:
PMC6234215
DOI:
10.1038/s41419-018-1173-x
[Indexed for MEDLINE]
Free PMC Article

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