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Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis
Author(s) -
Zamzami Naoufal,
Marchetti Philippe,
Castedo Maria,
Hirsch Tamara,
Susin Santos A.,
Masse Benjamin,
Kroemer Guido
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00280-3
Subject(s) - mitochondrial permeability transition pore , apoptosis , microbiology and biotechnology , membrane potential , mitochondrion , chemistry , biophysics , programmed cell death , transmembrane protein , biology , biochemistry , receptor
In a number of experimental systems, the early stage of the apoptotic process, i.e. the stage which precedes nuclear disintegration, is characterized by the breakdown of the inner mitochondrial transmembrane potential ( ΔΨ m ). Here we address the question as to whether mitochondrial permeability transition (PT) pores may account for the ΔΨ m dissipation in lymphocyte apoptosis. Drugs known for their PT‐inhibitory potential (bongkrekic acid, cyclosporin A, and the non‐immunosuppressive cyclosporin A analogue N ‐methyl‐Val‐4‐cyclosporin A) are capable of preventing the apoptotic ΔΨ m disruption. Moreover, pharmacological modulation of PT‐mediated ΔΨ m dissipation can prevent apoptosis. Thus, while suppressing the ΔΨ m disruption, bongkrekic acid also inhibits the apoptotic chromatinolysis. In conclusion, these data are compatible with the hypothesis that apoptotic ΔΨ m disruption is mediated by the formation of PT pores and that PT‐mediated ΔΨ m disruption is a critical event of the apoptotic cascade.