1. Death receptor-mediated apoptosis and the liver
Jung-Hwan Yoon, Gregory J Gores 
Journal of Hepatology 
Volume 37, Issue 3, Pages (September 2002)
DOI: /S (02)00209-X

2. Fig. 1
Structures of death receptors. Death receptors are type-I transmembrane proteins with an extracellular ligand-binding N-terminal region containing cysteine-rich domains, a membrane spanning region, and a C-terminal intracellular tail containing the death domain essential for signaling apoptosis. TNF-R1, tumor necrosis factor receptor 1; TRAIL-R1/2, tumor necrosis factor related apoptosis inducing ligand receptors 1 and 2.
Journal of Hepatology  , DOI: ( /S (02)00209-X)

3. Fig. 2
Death receptor-mediated apoptosis. Oligomerization of death receptors leads to recruitment of the cytoplasmic adapter protein FADD (Fas associated death domain). FADD contains a death effector domain that mediates the recruitment of caspases through the association with a corresponding death effector domain in the prodomain of the inactive initiator caspases, caspase 8 and 10. Active caspase 8/10 cleaves the pro-apoptotic BH3 domain only protein Bid. This truncated Bid translocates to mitochondria inducing release of cytochrome c from mitochondria. The cytosolic cytochrome c binds to Apaf-1, facilitating recruitment of caspase 9 in a protein complex referred to as the apoptosome. Active caspase 9 cleaves effector caspases, caspase 3 and 7, causing apoptosis.
Journal of Hepatology  , DOI: ( /S (02)00209-X)

4. Fig. 3
Inhibition of death receptor-mediated apoptosis. c-FLIP (FLICE-inhibitory proteins) can bind to the DISC (death-inducing signaling complex) and either competitively inhibit procaspase 8 recruitment to the DISC or prevent proteolytic processing of caspase 8. Anti-apoptotic Bcl-2 family members, Bcl-2, Bcl-XL, Mcl-1, etc. can associate and form complexes with pro-apoptotic Bcl-2 members, thereby inhibiting the release of cytochrome c. Inhibitors of apoptosis proteins (IAPs), XIAP, c-IAP-1 and c-IAP-2, bind procaspase 9 and prevent its activation, and can also directly bind and inhibit active caspases. HSP (heat shock protein) 27 binds to cytochrome c, and HSP70 and HSP90 bind to Apaf-1, resulting in the inhibition of apoptosome formation.
Journal of Hepatology  , DOI: ( /S (02)00209-X)

5. Fig. 4
TNF-R1-mediated apoptotic and anti-apoptotic pathways. Engagement of TNF-R1 by TNF-α activates caspase 8/10 and JNK (c-Jun NH2-terminal kinase), leading to apoptosis. TNF-R1 activation can also lead to phosphorylation of the NF-κB inhibitory protein, allowing NF-κB to translocate to the nucleus and initiate transcription of target genes, most of which are involved in survival pathways. These survival proteins can inhibit the JNK pathway and prevent caspase 8/10 activation.
Journal of Hepatology  , DOI: ( /S (02)00209-X)

6. Fig. 5
Therapeutic inhibition of apoptosis in the liver. Inhibition of hepatocyte apoptosis may be therapeutically beneficial in many liver diseases.
Journal of Hepatology  , DOI: ( /S (02)00209-X)

7. Fig. 6
Therapeutic induction of apoptosis in the liver. The enhanced sensitivity of virally infected hepatocytes to TRAIL-induced apoptosis could potentially be therapeutically useful for removing hepatocytes bearing covalently closed circular HBV DNA or HCV RNA. Selective induction of apoptosis in activated HSCs (hepatic stellate cells) via gliotoxin- or TRAIL-induced apoptotic signaling may also be an anti-fibrotic therapeutic strategy.
Journal of Hepatology  , DOI: ( /S (02)00209-X)

8. Fig. 7
Linking hepatocyte apoptosis to liver fibrosis. Hepatocyte apoptosis results in the generation of apoptotic bodies. Phagocytosis of apoptotic bodies by hepatic stellate cell (HSC) stimulates the expression of TGF-β and collagen in HSC, leading to liver fibrosis.
Journal of Hepatology  , DOI: ( /S (02)00209-X)