Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis

Abstract

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.

Keywords

Mitochondrial permeability transition poreApoptosisCell biologyMembrane potentialMitochondrionChemistryBiophysicsProgrammed cell deathTransmembrane proteinBiologyBiochemistryReceptor

MeSH Terms

AnimalsApoptosisBongkrekic AcidCyclosporineCyclosporinsDexamethasoneFemaleImmunosuppressive AgentsIntracellular MembranesLymphocytesMembrane PotentialsMiceMiceInbred BALB CMitochondriaPermeabilitySpleenStructure-Activity Relationship

Affiliated Institutions

Centre National de la Recherche Scientifique FR

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Publication Info

Year: 1996
Type: article
Volume: 384
Issue: 1
Pages: 53-57
Citations: 439
Access: Closed

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APA Style

                            
                                
                                    Naoufal Zamzami, 
                                
                                    Philippe Marchetti, 
                                
                                    Maria Castedo
                                
                                et al.
                            
                            (1996). 
                            Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis. 
                            FEBS Letters
                            , 384
                            (1)
                            , 53-57.
                            https://doi.org/10.1016/0014-5793(96)00280-3
                        

Identifiers

DOI: 10.1016/0014-5793(96)00280-3
PMID: 8797802

Data Quality

Data completeness: 86%