title: Induction of apoptosis by valinomycin: mitochondrial permeability transition causes intracellular acidification.
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.
authors: CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
authors: I J
authors: IJ
authors: Furlong
authors: C
authors: C
authors: Lopez Mediavilla
authors: R
authors: R
authors: Ascaso
authors: A
authors: A
authors: Lopez Rivas
authors: M K
authors: MK
authors: Collins
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D001865:Bongkrekic Acid / Q000494:pharmacology; D002460:Cell Line; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010539:Permeability; D014634:Valinomycin / Q000494:pharmacology*
chemical_list: D007476:Ionophores; D001865:Bongkrekic Acid; D014634:Valinomycin