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Unformatted text preview: s of the Bcl-2 family act at mitochondria,
which play a central role in controlling programmed cell death ( Figure
17.8). When activated, Bax and Bak form oligomers in the mitochondrial
outer membrane. Formation of these Bax or Bak oligomers leads to the
release of cytochrome c f rom the mitochondrial intermembrane space,
either by forming pores or by interacting with other mitochondrial outer
membrane proteins. The release of cytochrome c from mitochondria then
triggers caspase activation. In particular, the key initiator caspase in mammalian cells (caspase-9) is activated by forming a complex with Apaf-1 in
the apoptosome. In mammals, formation of this complex also requires
cytochrome c. Under normal conditions of cell survival, cytochrome c is
localized to the mitochondrial intermembrane space (see Figure 11.10)
while Apaf-1 and caspase-9 are found in the cytosol, so caspase-9 remains
inactive. Activation of Bax or Bak results in the release of cytochrome c to
the cytosol, where it binds to Apaf-1 and triggers apoptosome formation
and caspase-9 activation.
Caspases are also regulated...
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