The article by Philippe Marchetti et al. investigates the role of mitochondrial permeability transition (PT) in the apoptotic process. The authors use bongkrekic acid (BA), a specific inhibitor of PT, to study the effects of PT inhibition on apoptosis in a model system of glucocorticoid-induced thymocyte death. They find that BA not only prevents the early stage of ΔΨm disruption but also inhibits a number of subsequent apoptotic events, including depletion of nonoxidized glutathione, generation of reactive oxygen species, translocation of NFκB, exposure of phosphatidylserine residues, cytoplasmic vacuolization, chromatin condensation, and oligonucleosomal DNA fragmentation. Additionally, BA is effective in inhibiting p53-dependent thymocyte apoptosis induced by DNA damage. The study suggests that PT is a central coordinating event in the apoptotic cascade, and that it occurs secondary to the activation of certain cysteine and serine proteases. The findings highlight the importance of PT in the regulation of apoptosis and provide insights into the hierarchical control points of the apoptotic process.The article by Philippe Marchetti et al. investigates the role of mitochondrial permeability transition (PT) in the apoptotic process. The authors use bongkrekic acid (BA), a specific inhibitor of PT, to study the effects of PT inhibition on apoptosis in a model system of glucocorticoid-induced thymocyte death. They find that BA not only prevents the early stage of ΔΨm disruption but also inhibits a number of subsequent apoptotic events, including depletion of nonoxidized glutathione, generation of reactive oxygen species, translocation of NFκB, exposure of phosphatidylserine residues, cytoplasmic vacuolization, chromatin condensation, and oligonucleosomal DNA fragmentation. Additionally, BA is effective in inhibiting p53-dependent thymocyte apoptosis induced by DNA damage. The study suggests that PT is a central coordinating event in the apoptotic cascade, and that it occurs secondary to the activation of certain cysteine and serine proteases. The findings highlight the importance of PT in the regulation of apoptosis and provide insights into the hierarchical control points of the apoptotic process.