Fig. 6

Summary mechanism of Δψ_m depolarization enhances TRAIL-induced cell death through inhibition of BIRC5. Proposed mechanism depicting the interplay of Δψ_m and TRAIL resulting in increased induction of apoptosis in KGN cells. In viable and metabolically active cells, mitochondria (green) retain cytochrome c (red), however upon depolarization by either FCCP, or TRAIL (violet) binding with its receptors DR4/5 (purple), cytochrome c is released into the cytosol. In response to TRAIL activation of the DR4/5 intracellular death domain (DD) to form FADD and activate the pro-apoptotic caspase cascade, an upregulation of the inhibition of apoptosis protein family member, BIRC5 (blue), is induced, maintaining cell survival. In cells pretreated with FCCP, or those following a knockdown of BIRC5 expression, pro-apoptotic signals overcome pro-survival signaling to induce apoptosis, suggesting an essential role for Δψ_m in the opposition of pro-apoptotic signals