Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss

Treatment of cells with the HIV drugs ritonavir, saquinavir, or nelfinavir (Nfv) inhibits apoptosis induced by a variety of stimuli. Because these dru gs are protease inhibitors, they have been postulated to inhibit apoptosis by blocking caspase activity. This study shows that Nfv has no effect on ca spase activity or on the transcription or synthesis of a variety of apoptos is regulatory molecules. Instead, Nfv inhibits mitochondrial transmembrane potential loss (Delta psi (*)(m)) and the subsequent release of apoptotic, mediators. Consequently, the antiapoptotic effects of Nfv are restricted to apoptotic pathways that involve Delta psi (m). (C) 2001 by The American So ciety of Hematology.