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In-Depth Information
Live
Die
Smac
AIF
Bax
Bcl-2
cytochrome c
active Bad
inactive Bad
Bcl-x
Smac
Bax
IAP
Bcl-x
cytochrome c
Apaf-1
Apaf-1
Bcl-x
APOPTOSOME
cyt c
Apaf-2
pro-caspase-9
IAP
pro-caspase-9
caspase-9
pro-caspase-3
caspase-3
CAD
ICAD-CAD
FIGURE 7.27 The molecular state of a neuron that permits it to survive or leads it to death. (Left) The
living cell contains mitochondria that are preserved in a nonpermeable state due to the presence of an anti-
apoptotic regulator, Bcl-2. A second anti-apoptotic regulator, Bcl-x, complexes with Apaf-1, preventing the
activation of caspase-9. Bcl-x also binds to a pro-apoptotic regulator, Bax, and prevents it from influencing
the mitochondrion. A different pro-apoptotic regulator, Bad, is inactive, having been phosphoryated by neu-
rotrophin-elicited kinase activity. IAP binds to pro-caspase-9, and this also serves to prevent activation. A
nuclease that is responsible for DNA fragmentation, caspase-activated deoxyribonuclease (CAD), is bound
by its inhibitor, ICAD. (Right) In dying neurons, Bad becomes active when it is dephosphorylated, and it
binds to Bcl-x. This permits Bax to associate with the mitochondrion, leading to the release of cytochrome c,
AIF, and Smac. It also permits Apaf-1 to form an apoptosome with cyt c , process caspase-9, and activate
caspase-3. Smac binds to IAP, which also permits the processing of pro-caspase-9. One target of caspase-3 is
ICAD, leading to the release of CAD, and the fragmentation of DNA. In a caspase-independent pathway, AIF
also enters the nucleus and fragments DNA.
 
 
 
 
 
 
 
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