1. Lucifer's Labyrinth—Ten Years of Path Finding in Cell Death
Pascal Meier, Karen H. Vousden 
Molecular Cell 
Volume 28, Issue 5, Pages (December 2007)
DOI: /j.molcel
Copyright © 2007 Elsevier Inc. Terms and Conditions

2. Figure 1
Intrinsic and Extrinsic Pathways of Caspase Activation and Apoptosis
The intrinsic pathway is activated when BH3-only proteins cause oligomerization of Bax or Bak, which triggers mitochondrial release of apoptogenic factors such as cyt-c and IAP antagonists. Cyt-c subsequently triggers apoptosome assembly and activation of the caspase cascade. The extrinsic pathway involves oligomerization of death receptors by their ligands, resulting in recruitment and activation of caspase-8. Caspase-8 can execute apoptosis either directly, through cleavage of caspase-3, or indirectly, by cleaving Bid, which then translocates to mitochondria to initiate the intrinsic pathway. Red-circled numbers indicate points of therapeutic intervention strategies aimed at (1) reactivating p53, (2) targeting antiapoptotic Bcl-2 proteins, (3) neutralizing IAPs, and (4) activating death receptors.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2007 Elsevier Inc. Terms and Conditions

3. Figure 2 Two Models for the Activity of BH3-Only Proteins in Apoptosis
In model 1 (indirect activation), all BH3 proteins solely function to inactivate the antiapoptotic Bcl-2 family members, although the specificity of the interactions is distinct. Thus, certain BH3-only proteins, like Bid, Bim, and Puma, can inhibit all the antiapoptotic proteins and are therefore more potent than BH3 proteins such as Noxa, which only targets a subset of the antiapoptotic Bcl-2 family. In this model, binding of the BH3 proteins releases and activates Bax and Bak to drive mitochondrial membrane permeabilization. In model 2 (direct activation), the BH3 proteins fall into two groups. The “activator” BH3 proteins (Bid, Bim, and Puma) directly activate Bax and Bak and are held inactive through interaction with the antiapoptotic proteins. The “enabler” BH3 proteins function to displace the activators from these interactions.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2007 Elsevier Inc. Terms and Conditions

4. Figure 3 Death and Survival Functions of Autophagy
Autophagy plays a key role in the response to metabolic stress by allowing survival under conditions of nutrient starvation. However, extensive autophagy may also contribute to autophagic cell death that may occur in concert with, or even as part of, an apoptotic response. Failure to maintain survival through autophagy can also result in the activation of necrotic cell death. Another function of autophagy is the removal of damaged organelles such as mitochondria, an activity that can protect from both the accumulation of genetic damage and the release of apoptogenic factors, thereby inhibiting apoptosis. As indicated, the complex interplay between the death and survival responses to autophagy leads to equally complex effects on tumor promotion and inhibition, and it remains obscure whether modulating autophagy is of patient benefit.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2007 Elsevier Inc. Terms and Conditions