APOPTOSIS

Nur Signa Aini Gumilas

HISTOLOGY DEPT
 REFERENCES

• Alberts, B., Johnson, A., Lewis, J., Raff, M., et

al. 2007. Molecular Biology of The Cell 5th
Edition. Garland Science.
 LEARNING OBJECTIVE
• Apoptosis
– Extrinsic pathway
– Intrinsic pathway
– Regulation of apoptosis
• Necrosis
 Introduction
• Apoptosis  programmed cell death
• Characteristic morphological changes :
– Shrink & condense
– The cytoskeleton collapses
– The nuclear envelope disassembles
– The nuclear chromatin condenses & break up into
fragments
– Apoptotic bodies  cells break up into membrane-
enclosed fragments
– Without causing a damaging inflammatory response.
• Contrast to apoptosis  cell necrosis  cells
that die accidentally in response to an acute
insult  trauma, lack of blood supply.
• Characteristic cell necrosis :
– Cell swell & burst
– Spilling their contents over their neighbors
– Eliciting an inflammatory response
Apoptosis vs necrosis
Necrosis
Apoptosis
Apoptotic cells are phagocytosed
by macrophages
 Apoptotic Function
• As a quality-control process in development
• Eliminating cells that are abnormal,
misplaced, nonfunctional or potentially
dangerous.
•  Animal cells can recognize damage in their
various organelles  apoptosis
 Apoptosis Depends on an Intracellular
Proteolytic Cascade that is Mediated by Caspase
• The intracellular machinery responsible for
apoptosis  caspase (protease)
• Procaspase/inactive precursor  active 
caspases
• Initiator procaspases : act at the start of
proteolitic cascade
• Executioner procaspases : downstream of
initiator procaspases  cleave & activate
other executioner procaspase (target protein)
How is the procaspase in cascade activated?

•  Initiator procaspases (a caspase

recruitment domain/CARD)  assemble with
adaptor protein  activation complex 
initiator procaspase  cleave each other
 2 pathway can activate a caspase
cascade

• Extrinsic pathway
• Intrinsic pathway
 Extrinsic pathway
The extrinsic pathway of apoptosis activates through Fas death receptors
 Intrinsic Pathway
• The intrinsic pathway of apoptosis depends on mitochondria
• Intrinsic pathway  release of cytochrome
 Bcl2 protein regulate the intrinsic
pathway of apoptosis
• Bcl2 protein  a major class of intracellular
regulators of apoptosis
– Bcl2 proapoptotic
– Bcl2 antiapoptotic
• The role of BH123 proapoptotic Bcl2 protein
(mainly Bax & Bak) in the release of mitochondrial
intramembrane proteins in the intrinsic pathway of
apoptosis
 The absence of an apoptotic stimulus

How pro-apoptotic
BH3-only and anti
apoptotic Bcl2
proteins regulate the
intrinsic pathway of
apoptosis?
In the presence of an apoptotic stimulus
Extracellular survival factors inhibit
apoptosis in various ways
excessive or insufficient
apoptosis can contribute
to disease

Ex : autoimun disease, cancer

THANK YOU