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 drugs are protease inhibitors, they have been postulated to inhibit apoptosis by blocking caspase activity. This study shows that Nfv has no effect on caspase activity or on the transcription or synthesis of a variety of apoptosis regulatory molecules. Instead, Nfv inhibits mitochondrial transmembrane potential loss (Δψ m ) and the subsequent release of apoptotic mediators. Consequently, the antiapoptotic effects of Nfv are restricted to apoptotic pathways that involve Δψ m .