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

FEBS Letters

Masse, Benjamin¹  Marchetti, Philippe¹  Zamzami, Naoufal¹  Hirsch, Tamara¹  Susin, Santos A.¹  Castedo, Maria¹  Kroemer, Guido¹ 

[1] CNRS-UPR420, 19 rue Guy Môquet, B.P.8, F-94801 Villejuif, France

关键词: T lymphocyte;    Apoptosis;    Mitochondrial transmembrane potential;    Permeability transition;    Programmed cell death;   

DOI  :  10.1016/0014-5793(96)00280-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown