Figure 8. PB1-F2 Induces Apoptosis Acting through Components of the PTPC.

(A) ANT3 blocker BA inhibits PB1-F2-mediated sensitization of cells to apoptosis. A549 cells were transfected with PB1-F2 for 20 h and then treated with TNFα as indicated, either in the presence or absence of 50 μM BA. The cells were collected 8 h later and stained with M30 antibody to cleaved cytokeratin.

(B) Proposed models of PB1-F2 action during infection. During early stages of the infection, PB1-F2 localizes to mitochondria, where it interacts with ANT3 and VDAC and predisposes the mitochondria to permeability transition. Later in the infection, when more PB1-F2 is synthesized, and upon induction of antiviral apoptotic signaling pathways, the mitochondria undergo the permeability transition, which results in the induction of apoptosis. PB1-F2-induced mitochondrial permeabilization can proceed through three possible mechanisms, as indicated on the right graphic: (1) enhancement of the pore complex formation through direct interaction with ANT3 and VDAC1; (2) independent permeabilization of the inner and outer mitochondrial membranes with the help of ANT3 and VDAC1, respectively; and (3) direct permeabilization of the mitochondrial membranes.