Compromised mitochondrial function leads to increased cytosolic calcium and to activation of MAP kinases

摘要

We have investigated in rat pheochromacy- toma PC12 cells the activation of the mitogen-activated pro- tein kinases ERK1 and ERK2 by the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP). This treatment slowly decreases ATP levels to 30/100 of control, whereas the internal calcium level rises very rapidly to 250/100 of control, derived from internal stores. Tyrosine phosphorylation of ERK1 and ERK2 increases gradually, starting after 5 min of treatment, to reach a maximum at 30 min; the kinase activity reaches 250/100 when measured after 1 hr of treatment. The drop in ATP levels is slower still.