Induction of apoptosis by valinomycin: mitochondrial permeability transition causes intracellular acidification.
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.
Furlong
I J
IJ
CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
Lopez Mediavilla
C
C
Ascaso
R
R
Lopez Rivas
A
A
Collins
M K
MK
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*
D007476:Ionophores; D001865:Bongkrekic Acid; D014634:Valinomycin