Essential Cell Biology 5th edition

Control of Cell Numbers and Cell Size
641
Figure 18−38 Cells undergoing
apoptosis die quickly and cleanly.
Electron micrographs showing cells that
have died (A) by necrosis or (B and C)
by apoptosis. The cells in (A) and (B)
died in a culture dish, whereas the cell
in (C) died in a developing tissue and
has been engulfed by a phagocytic cell.
Note that the cell in (A) seems to have
exploded, whereas those in (B) and (C)
have condensed but seem relatively
intact. The large vacuoles seen in
the cytoplasm of the cell in (B) are a
variable feature of apoptosis. (Courtesy
of Julia Burne.)
(A)
(B)
10 µm
(C)
engulfed
dead cell
phagocytic cell
phagocytic cells called macrophages (see Figure 15–32B). These cells
engulf the apoptotic cell before its contents can leak out (Figure 18−38C).
This rapid removal of the dying cell avoids the damaging consequences of
cell necrosis, and it also allows the organic components of the apoptotic
cell to be recycled by the cell that ingests it.
ECB5 e18.37/18.38
The molecular machinery responsible for apoptosis, which seems to
be similar in most animal cells, involves a family of proteases called
caspases. These enzymes are made as inactive precursors, called
procaspases, which are activated in response to signals that induce apoptosis.
Two types of caspases work together to take a cell apart. Initiator
caspases cleave, and thereby activate, downstream executioner caspases,
which dismember numerous key proteins in the cell (Figure 18−39). One
executioner caspase, for example, targets the lamin proteins that form
the nuclear lamina underlying the nuclear envelope (see Figure 18–30);
this cleavage causes the irreversible breakdown of the nuclear lamina,
which allows nucleases to enter the nucleus and break down the DNA.
QUESTION 18–10
Why do you think apoptosis
occurs by a different mechanism
from the cell death that occurs in
cell necrosis? What might be the
consequences if apoptosis were not
achieved in so neat and orderly a
fashion, whereby the cell destroys
itself from within and avoids leakage
of its contents into the extracellular
space?
APOPTOTIC
STIMULUS
adaptorbinding
domain
protease
domain
initiator procaspase
cleavage
sites
inactive monomers
adaptor proteins
DIMERIZATION,
ACTIVATION,
AND CLEAVAGE
executioner procaspase
active
initiator
caspase
ACTIVATION
BY CLEAVAGE
active
executioner
caspase
CLEAVAGE OF
MULTIPLE
SUBSTRATES
APOPTOSIS
Figure 18−39 Apoptosis is mediated
by an intracellular proteolytic cascade.
An initiator caspase is first made as an
inactive monomer called a procaspase.
An apoptotic signal triggers the assembly
of adaptor proteins that bring together a
pair of initiator caspases, which are thereby
activated, leading to cleavage of a specific
site in their protease domains. Executioner
caspases are initially formed as inactive
dimers. Upon cleavage by an initiator
caspase, the executioner caspase dimer
undergoes an activating conformational
change. The executioner caspases then
cleave a variety of key proteins, leading to
apoptosis.