Opposite role of changes in mitochondrial membrane potential in different apoptotic processes

We have studied the role of changes in mitochondrial membrane potential (De lta Psi) in two widely-used models of apoptosis, such as dexamethasone-trea ted rat thymocytes and U937 human cells treated with tumor necrosis factor- alpha and cycloheximide. To dissipate Delta Psi, we used low concentrations of valinomycin, unable per se to induce apoptosis, and demonstrated that t he decline in Delta Psi exerts opposite effects in the two models. Indeed, in U937 cells, depolarization of mitochondria increased apoptosis, which de creased in rat thymocytes. This leads to the suggestion that disruption of Delta Psi plays opposite roles depending on the experimental model. In U937 cells, the drop of Delta Psi is a possible contributory cause for the apop totic process; in rat thymocytes, it could be a limiting factor. We propose that these opposite effects could be due to the different ATP requirement of each apoptotic pathway. (C) 2000 Federation of European Biochemical Soci eties.