FIGURE 1.

Proposed model for MNDA regulation of neutrophil apoptosis. Cytoplasmic relocation and cleavage of MNDA results in aggravation of mitochondrial dysfunction through promotion of proteasomal degradation of MCL-1. Activation of this novel nucleus-mitochondrion circuit would then accelerate execution of the apoptotic death program. Conversely, prevention of MNDA relocation and cleavage would prolong neutrophil survival by retarding apoptosis. The mechanisms by which bacterial components and/or inflammatory modulators could negatively influence MNDA relocation and cleavage and hence, interfere with this nuclear-mitochondrial circuit remains to be defined. Broken line indicates yet undefined mechanism.