FIGURE 6: Model of the T. gondii-mediated inhibition of the caspase-dependent intrinsic PCD pathway.

A cell-intrinsic pro-apoptotic signal leads via activation of pro-apoptotic Bcl-2 family members to MOMP and release of apoptogenic molecules including cytochrome c from mitochondria. Binding of cytochrome c to Apaf-1 and nucleotide exchange induce conformational changes that allow oligomerization of Apaf-1, caspase 9 recruitment and caspase activation. T. gondii inhibits the mitochondrial apoptotic pathway at least twofold: (i) by inhibition of MOMP [17, 30, 32, 37] and (ii) by inhibiting cytochrome c-triggered holo-apoptosome assembly (described herein). See main text for further details.

17. Hippe D, Lytovchenko O, Schmitz I, Lüder CG (2008). Fas/CD95-mediated apoptosis of type II cells is blocked by Toxoplasma gondii primarily via inter-ference with the mitochondrial amplification loop. Infect Immun 76(7): 2905-2912. http://dx.doi.org/10.1128/IAI.01546-07

30. Goebel S, Gross U, Lüder CG (2001). Inhibition of host cell apoptosis by Toxoplasma gondii is accompanied by reduced activation of the caspase cascade and alterations of poly(ADP-ribose) polymerase expression. J Cell Sci 114(Pt 19): 3495-3505. http://www.ncbi.nlm.nih.gov/pubmed/?term=11682609

32. Carmen JC, Hardi L, Sinai AP (2006). Toxoplasma gondii inhibits ultraviolet light-induced apoptosis through multiple interactions with the mitochondrion-dependent programmed cell death pathway. Cell Microbiol 8(2): 301-315. http://dx.doi.org/10.1111/j.1462-5822.2005.00622.x

37. Hippe D, Weber A, Zhou L, Chang DC, Hacker G, Luder CG (2009). Toxoplasma gondii infection confers resistance against BimS-induced apoptosis by preventing the activation and mitochondrial targeting of pro-apoptotic Bax. J Cell Sci 122(Pt 19): 3511-3521. http://dx.doi.org/10.1242/jcs.050963