TY - JOUR T1 - AMP-kinase Activation Alters Oxidant-induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.116.105494 SP - mol.116.105494 AU - Hicham Mahboubi AU - Antonis Koromilas AU - Ursula Stochaj Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/07/18/mol.116.105494.abstract N2 - Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK) which functions as a stress sensor and is transiently activated by adverse physiological conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, as the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, the abundance of translation initiation factors and cytoskeletal organization. Specifically, AMPK activation increased the stress-induced eIF2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of protein deacetylase HDAC6 was diminished. This loss of HDAC6 was accompanied by an increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation, but limits their fusion into larger granules. ER -