Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation.
In cells exposed to environmental stress, inhibition of translation initiation conserves energy for the repair of cellular damage. Untranslated mRNAs that accumulate in these cells move to discrete cytoplasmic foci known as stress granules (SGs). The assembly of SGs helps cells to survive under adverse environmental conditions. We have analyzed the mechanism by which hydrogen peroxide (H(2)O(2))-induced oxidative stress inhibits translation initiation and induces SG assembly in mammalian cells. Our data indicate that H(2)O(2) inhibits translation and induces the assembly of SGs. The assembly of H(2)O(2)-induced SGs is independent of the phosphorylation of eIF2α, a major trigger of SG assembly, but requires remodeling of the cap-binding eIF4F complex. Moreover, H(2)O(2)-induced SGs are compositionally distinct from canonical SGs, and targeted knockdown of eIF4E, a protein required for canonical translation initiation, inhibits H(2)O(2)-induced SG assembly. Our data reveal new aspects of translational regulation induced by oxidative insults.
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
Mohamed M
MM
Emara
Ken
K
Fujimura
Daniele
D
Sciaranghella
Victoria
V
Ivanova
Pavel
P
Ivanov
Paul
P
Anderson
D000818:Animals; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018384:Oxidative Stress; D010766:Phosphorylation; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D022661:RNA, Untranslated / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D006861:Hydrogen Peroxide