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Editorial
. 2015 Dec;62(6):1664-6.
doi: 10.1002/hep.28107. Epub 2015 Sep 30.

Acetaminophen knocks on death's door and receptor interacting protein 1 kinase answers

Maria Eugenia Guicciardi  1 , Gregory J Gores  1 , Hartmut Jaeschke  2
Affiliations
Editorial

Acetaminophen knocks on death's door and receptor interacting protein 1 kinase answers

Maria Eugenia Guicciardi et al. Hepatology. 2015 Dec.
No abstract available

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Figures

Figure 1
Figure 1. RIP1-regulated cell death pathways
Following binding of death receptors (TNF-R1, Fas, or TRAIL receptors) in cells with functional caspase 8, and in the presence of IAP (Inhibitor of Apoptosis Proteins) antagonism, which prevents RIP1 ubiquitination, RIP1 associates with the adaptor molecules FADD (Fas-Associated protein with Death Domain) and TRADD (TNF-R-Associated protein with Death Domain), and with caspase 8 triggering caspase 8-mediated apoptosis (left). When caspase 8 activity is inhibited, and in the presence of RIP3, binding of death receptors or toll-like receptors induces the formation of a signaling complex comprising RIP1, RIP3 and MLKL (named the necrosome), resulting in RIP1-RIP3-dependent necroptosis (center). APAP treatment triggers increase of cytosolic RIP1 and its translocation to mitochondria by a yet-to-be identified mechanism. RIP1 activation precedes and contributes to JNK activation, which results in RIP1-dependent, RIP3-independent necrotic hepatocyte death. How RIP1 regulates JNK activation is currently unknown (right).
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References

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