Apoptosis Supercedes Necrosis In Mitochondrial Dna-Depleted Jurkat Cells By Cleavage Of Receptor-Interacting Protein And Inhibition Of Lysosomal Cathepsin

In the present study, we used mitochondrial DNA-depleted Jurkat subclones (rho(0) cells) to demonstrate that Fas agonistic Ab (CH-11), at the concentrations that evoke apoptotic death of the parental Jurkat cells, induced necrosis mainly through generation of excess reactive oxygen species, lysosomal rupture, and sequential activation of cathepsins B and D, and in minor part through activation of receptor-interacting protein (RIP). In the rho(0) cells treated with CH-11, ATP supplementation converted necrosis into apoptosis by the formation of the apoptosome and subsequent activation of procaspase-3. In these ATP-supplemented rho(0) cells (ATP-rho(0)), generation of excess ROS and lysosomal rupture were still seen, yet cathepsins B and D were inactivated and RIP was degraded. The conversion of necrosis to apoptosis, RIP degradation, and cathepsin inactivation in ATP-rho(0) cells were blocked by caspase-3 inhibitors. Activities of cathepsins B and D in the lysate of necrotic rho(0) cells were inhibited by the addition of apoptotic parental Jurkat cell lysate. Thus, apoptosis may supercede necrosis.