INDUCTION OF APOPTOSIS BY VALINOMYCIN - MITOCHONDRIAL PERMEABILITY TRANSITION CAUSES INTRACELLULAR ACIDIFICATION

In order to determine whether disruption of mitochondrial function cou ld trigger apoptosis in murine haematopoietic cells, we used the potas sium ionophore valinomycin. Valinomycin induces apoptosis in the murin e pre-B cell line BAF3, which cannot be inhibited by interleukin-3 add ition or Bcl-2 over-expression. Valinomycin triggers rapid loss of mit ochondrial membrane potential. This precedes cytoplasmic acidification , which leads to cysteine-active-site protease activation, DNA fragmen tation and cell death. Bongkrekic acid, an inhibitor of the mitochondr ial permeability transition, prevents acidification and subsequent ind uction of apoptosis by valinomycin.