Apoptosis

Definition
• A pathway of cell death that is induced by a tightly regulated suicide
program in which cells destined to die activate intrinsic enzymes that
degrade the cells’ own nuclear DNA and nuclear and cytoplasmic
proteins

• Also known for its name “falling off”

 What Causes Apoptosis?
1. Physiologic Apoptosis – under
normal development of an
organism.
2. Immune system apoptosis –
Eliminates excess leukocytes and
lymphocytes left at the end of
immune response that could
cause autoimmune diseases.
3. Apoptosis in pathologic
conditions – eliminates damage
cell or cells with severe DNA
damage.
Mechanism of Apoptosis
• Apoptosis results from the activation of enzymes called caspases
(cysteine proteases that cleave proteins after aspartic residues)
• Caspases are inactive proenzymes, or zymogens that must undergo
enzymatic cleavage to become active and therefore becomes a
marker for cells undergoing apoptosis.
• There are two processes during apoptosis: the initiation phase,
which some caspases become catalytically active; the execution
phase, which other caspases trigger the degradation of critical
cellular components.
Initiation Phase
• Pathways of Apoptosis
1. Intrinsic (Mitochondrial) Pathway
2. Extrinsic (Death Receptor-Initiated) Pathway
Pathways of Apoptosis
• Intrinsic Pathway
- This pathway increases permeability
of mitochondrial outer membrane results to
release of death-inducing (proapoptotic Bax
and bak) molecules from the mitochondrial
intermembrane space into the cytoplasm.
- In an unhealthy cell, the mitochondria
releases the protein cytochrome C into the
cytoplasm that initiates suicide program by
activating caspase 9 leading to nuclear
fragmentation then apoptosis. .
Pathways of Apoptosis
• Extrinsic Pathway
- This pathway is initiated by
engagement of plasma membrane
death receptors on a variety of cells.
- The TNF receptor family
contains a cytoplasmic domain
involved in protein-protein interaction
called Death domain which is
essential for delivering apoptotic
signals.
Pathway of Apoptosis
• The extrinsic and intrinsic pathways of apoptosis involve
fundamentally different molecules for their initiation, but there
may be interconnections between them.
• The combined activation of both pathways delivers a fatal blow
to the cells.
Execution Phase of Apoptosis
• This phase involves the convergence of the two initiating
pathways(mitochondrial and death receptor) to a cascade of caspase
activation that would mediate the FINAL PHASE of apoptosis. This is
set in motion by rapid and sequential activation of the executioner
caspases ( -3 and -6) that act on many cellular components:
• Induces cleavage of DNA
• Degradation of nuclear matrix  fragmentation of nuclei
 Removal of Dead Cells
• Formation of apoptotic bodies breaks
cells up into “bite-sized” fragments
and would undergo several changes in
their membranes that would render
them edible for phagocytes
• In apoptotic cells, phosphatidylserine
(PS), is a phospholipid of the plasma
membrane, recognized by
macrophages and activates ingestion
of the cell’s remains without release of
its intracellular constituents, thus
avoiding an inflammatory reaction.