1. Mitochondrial Inhibition by Sodium Azide Induces Assembly of eIF2α Phosphorylation-Independent Stress Granules in Mammalian Cells
- Author
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Nina Eiermann, Georg Stoecklin, and Bogdan Jovanovic
- Subjects
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone ,Mammals ,stress granules ,integrated stress response ,translation ,mitochondrial stress ,sodium azide ,Eukaryotic Initiation Factor-2 ,Organic Chemistry ,RNA-Binding Proteins ,Saccharomyces cerevisiae ,General Medicine ,Cytoplasmic Granules ,Stress Granules ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Animals ,Phosphorylation ,Physical and Theoretical Chemistry ,Sodium Azide ,Molecular Biology ,Spectroscopy - Abstract
Mitochondrial stress is involved in many pathological conditions and triggers the integrated stress response (ISR). The ISR is initiated by phosphorylation of the eukaryotic translation initiation factor (eIF) 2α and results in global inhibition of protein synthesis, while the production of specific proteins important for the stress response and recovery is favored. The stalled translation preinitiation complexes phase-separate together with local RNA binding proteins into cytoplasmic stress granules (SG), which are important for regulation of cell signaling and survival under stress conditions. Here we found that mitochondrial inhibition by sodium azide (NaN3) in mammalian cells leads to translational inhibition and formation of SGs, as previously shown in yeast. Although mammalian NaN3-induced SGs are very small, they still contain the canonical SG proteins Caprin 1, eIF4A, eIF4E, eIF4G and eIF3B. Similar to FCCP and oligomycine, other mitochodrial stressors that cause SG formation, NaN3-induced SGs are formed by an eIF2α phosphorylation-independent mechanisms. Finally, we discovered that as shown for arsenite (ASN), but unlike FCCP or heatshock stress, Thioredoxin 1 (Trx1) is required for formation of NaN3-induced SGs.
- Published
- 2022
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