Cell death is the basic process. Various genes are related to it along with two basic pathways. Apoptosis is needed to avoid some basic as well as lethal diseases.

1. APOPTOSIS
MANSI PATEL
ROLL NO. 09
BIOTECHNOLOGY (PREVIOUS)
B.R.D. SCHOOL OF BIOSCIENCE

2. CONTENT
Genes involved in PCD
Caspases
Central regulators of apoptosis:
The bcl-2 family
 Two major pathways :
Intrinsic pathway
Extrinsic pathway
Why suicide?
Diseases
Applications
References

3. Genes involved in PCD
ced=cell death defective gene
The genes ced-3 and ced-4 = developmental
cell death.
ced-9 =regulation of ced-3 and ced-4
nuc-1 encodes for nucleases that digest the
DNA of dead cell.

4. Cont…
ced-3 = member of specialized family of cell
death protease called CASPASES
ced-4 =scaffolding/adaptor protein (ced-3*)
ced-9 = member of Bcl-2 family of cell death
regulator

5. Programmed cell death in C. elegans

6. CASPASES
Cystein-dependent aspartate-specific proteases
 Ced-3 is the proteotype of a family of proteases
known as caspases.
 Caspases have cysteine (C) residues at their active
sites and cleave after aspartic acid (Asp) residues in
their substrate proteins.

7. Types of caspases
Initiator
Autoactivate
Caspase-9
Effector
Inactive
procaspase-3
Caspase-3

9. Bcl-2 proteins
B cell Lymphoma-Bcl/bcl
Bcl-2 inhibits apoptosis.

10. Central Regulators of Apoptosis: The Bcl-2
Family

12. Extrinsic Pathway
 Death receptors= triggres apoptotic death
 Receptor-ligand binding
 Turn on pathway
 Well-characterized death recptor is called
FAS
 Triggers set of downstream processes.

13. Extrinsic
pathway:
Programmed cell death

14. Mitochondria
Cytochrome c release
Pro-caspase 9 cleavage
Pro-execution caspase (3) cleavage
Caspase (3) cleavage of cellular proteins,
nuclease activation,
etc.
Death
BAX
BAK
BOK
BCL-Xs
BAD
BID
B IK
BIM
NIP3
BNIP3
BCL-2
BCL-XL
BCL-W
MCL1
BFL1
DIVA
NR-13
Several
viral
proteins
Intrinsic pathway:
Programmed cell death

15. Activation of Caspases

16. Intrinsic pathway of apoptosis
Such death signals are routed via mitochondria in a series of
events known as Intrinsic pathway of apoptosis.
Death signals within the cell triggers the activation of
proapoptotic proteins such as Bax.
When activated, Bax forms a oligomers in the outer
membrane of the mitochondria.
 Formation of oligomers leads to release of cytochrome c
from mitochondrial intermembrane space, either by forming
the pore or by binding with other membrane proteins.

17. contd…
 While in the mitochondria, cytochrome c involved in
cellular respiration, but in cytosol, cytochrome c drives the
cell into apoptosis.
 Cytochrome c binds to the cytosolic protein (Apaf-1),to
form a complex structure called as Apoptosome.
 Another protein (Caspase 9) is now activated by forming a
complex with Apaf-1in the Apoptosome.
 The accidental activation of caspases could result
in apoptosis, but this is prevented by IAP
(Inhibitor apoptosis) protein.

18. Intrinsic pathway:
Programmed cell death

19. Why should a cell commit suicide?
Apoptosis is needed to destroy cells
Examples:
Cells infected with viruses
Cells of the immune system
Cells with DNA damage
Cancer cells

20. Immunity (eliminates dangerous cells):
Self antigen
recognizing cell
Organ size (eliminates excess cells):

21. Neuronal death caused by loss of proper
connections
Neuronal dysfunction or damage results in loss of
synapses or loss of cell bodies
(synaptosis, can be reversible; Apopsosis is irreversible)
PARKINSON'S DISEASE
ALZHEIMER'S DISEASE
HUNTINGTON'S DISEASE etc.
Apoptosis: role in disease

22. Survival signals for Nerve Cell

25. APPLICATIONSOFAPOPTOSIS
 Apoptosis technology has great commercial as
well as academic applications,.....
 To understand the developmental regulation
of multicellular organisms and morphogenesis
 To study diseases(ALZIMERS & PARKINSONS
DISEASES), immunosuppression or an effect
of trauma
(STROKE & HEART ATTACK),
The pathological suppression of apoptosis is
also important for cancer and viral infections.

26. Cont…
 To maintain several industrially useful cell lines
(FOR PRODUCTION OF ANTIBODIESAND
VACCINES)which require costly growth factors.
 They could be maintained longer with less
effective cell deaths by altering the genetic
make up of these cells.

27. REFERENCES
 Cell biology –Thomson D. Pollard
(833-850,ch-46)
Fundamental of immunology-William E. Paul
( 6th edition)(834-
836)(ch-27)
 CELLS - Lewin(5th edition)
 CELL BIOLOGY- Channarayappa
 http://www.intechopen.com/books/apoptosis-
and-medicine/extrinsic-and-intrinsic-apoptosis-
signal-pathway-review