Figure 4.

NAD+ vs. PAR Polymers in Caspase-Independent Cell Death. This cartoon depicts the dichotomy in the caspase-independent cell death cascade (exaggerated for clarity as significant overlap likely occurs in vivo). There is cross talk between PARP-1 and NAD+ depletion, but NAD+ depletion caused glycolytic inhibition, mitochondrial depolarization, AIF translocation, and cell death without PARP-1 activation. Although PARP-1 activation causes PAR polymer formation, AIF translocation and cell death does not necessarily follow. The reviewed literature suggests that NAD+ depletion is necessary and plays the role of executioner in the caspase-independent cell death pathway.