Changes in mitochondrial membrane potential and mitochondrial mass occur independent of the activation of caspase-8 and caspase-3 during CD95-mediated apoptosis in peripheral blood T cells.

Although death receptor pathway and mitochondrial pathways of apoptosis are connected through Bid cleavage, such activation of mitochondrial pathway by death receptor signaling is observed in type II cells and not in type I cells (peripheral blood T cells). Furthermore, activation of mitochondria via Bid is associated with release of cytochrome c and caspase-9 activation. In this study we demonstrate that anti-CD95-induced apoptosis in T cells is associated with both depolarization of mitochondrial membrane potential (Delta(psi)m) and increase in mitochondrial mass and activation of caspase-8 and caspase-3 but without caspase-9 activation. Furthermore, changes in mitochondrial membrane potential and mitochondrial mass by anti-CD95 monoclonal antibodies were unaffected by inhibitors of caspase-8 and caspase-3, suggesting that anti-CD95-induced changes in Delta(psi)m and mitochondrial mass are independent of caspase-8 and caspase-3 activation.