Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) induces initiation factor 2 alpha phosphorylation and translation inhibition in PC12 cells

We have investigated the effect of the mitochondrial uncoupler carbonyl cya nide p-trifluoromethoxyphenylhydrazone (FCCP) on protein synthesis rate and initiation factor 2 (eIF2) phosphorylation in PC12 cells differentiated wi th nerve growth factor. FCCP treatment induced a very rapid 2-fold increase in intracellular Ca2+ concentration that was accompanied by a strong prote in synthesis rate inhibition (68%), The translation inhibition correlated w ith an increased phosphorylation of the alpha subunit of eIF2 (eIF2 alpha) (25% vs. 7%, for FCCP-treated and control cells, respectively) and a 1.7-fo ld increase in the double-stranded RNA-dependent protein kinase activity, N o changes in the PKR endoplasmic reticulum-related kinase or eIF2 alpha pho sphatase were found, Translational regulation may play a significant role i n the process triggered by mitochondrial calcium mobilization. (C) 2001 Fed eration of European Biochemical Societies. Published by Elsevier Science B. V. All rights reserved.