Induction of apoptosis by valinomycin: mitochondrial permeability transition causes intracellular acidification.

I J Furlong, C Lopez Mediavilla, R Ascaso, A Lopez Rivas, M K Collins

Index: Cell Death Differ. 5 , 214, (1998)

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Abstract

In order to determine whether disruption of mitochondrial function could trigger apoptosis in murine haematopoietic cells, we used the potassium ionophore valinomycin. Valinomycin induces apoptosis in the murine pre-B cell line BAF3, which cannot be inhibited by interleukin-3 addition or Bcl-2 over-expression. Valinomycin triggers rapid loss of mitochondrial membrane potential. This precedes cytoplasmic acidification, which leads to cysteine-active-site protease activation, DNA fragmentation and cell death. Bongkrekic acid, an inhibitor of the mitochondrial permeability transition, prevents acidification and subsequent induction of apoptosis by valinomycin.