Fig. 4.

F-actin rearrangements and cellular morphogenesis during apoptosis. (A) Early in intrinsic apoptosis, mitochondrial outer membrane permeabilization (MOMP) enables cytochrome c (cyto c) release into the cytosol, and F-actin is polymerized and reorganized at a juxtanuclear site containing the permeabilized mitochondria. These F-actin-rich territories promote the sequestration of cytosolic cyto c and facilitate interactions between apoptosome components. (B) As apoptosis progresses, cell rounding and chromatin condensation occur. The juxtanuclear F-actin-rich territory functions as a subcellular compartment that clusters multiple pro-apoptotic constituents and serves to couple the apoptosome biogenesis process to the activation of the caspase cascade. (C) Executioner caspases clustered within the territories are physically protected from caspase inhibitors and become enzymatically active. They eventually reach quantities that can overcome the inhibitors, escape the territory, and execute a sudden breakdown of the cell leading to the characteristic morphological features of apoptosis such as nuclear fragmentation and cortical membrane collapse. Note that the stoichiometry of organelles and macromolecules shown in the figure (e.g., mitochondria, cyto c, apoptosomes, caspases) are not drawn to scale.