the above presentation explain the process of programmed cell death in the cells.

1. APOPTOSIS

2. What is apoptosis.
A energy dependent mechanism of programmed cell
death, in which cells are destined to die by activating
enzymes that degrade cells own nuclear DNA and
cytoplasmic proteins.
Molecular mechanism of apoptosis is discovered by
Hortviz in 1990.

3. Apoptosis vs necrosis
Apoptosis Necrosis
 Cell shrinkage cell swelling
 Pyknosis and karyorrhexis karyolysis, pyknosis and karyorrhexis
 Intact cell membrane & blebbing disrupted cell membrane
occurs.
 Cytoplasm retained in apoptotic cytoplasm released
bodies.
 No inflammation. inflammation usually present
 Energy dependent cell death. Energy independent cell death

4. Fig:- Apoptosis

5. Purpose of apoptosis.
 It is essential for embryogenesis, metamorphosis and aging.
 To prevent cancer.
 To remove vestigial organs.
 As defence mechanism.
Chemical changes occurs during apoptosis:-
 Chemical changes on the surface of apoptotic cells or bodies serves as a marker of these cells
to recognize by surrounding cells and macrophages and engulf them.
 The negatively charged phospholipid phosphatidylserine is normally located in the inner
leaflet of the plasma membrane, but it flips to the outer leaflet in apoptotic, and work as a
marker of these cells.

6. Mechanism of apoptosis:-
 The mechanism of apoptosis are highly complex and regulated, involving an engery-
dependent cascade of molecular events.
 The classical caspase dependent apoptosis is initiated either by extrinsic or intrinsic factors.
 There are two main caspase dependent apoptotic pathways:-
1) The extrinsic or death receptor pathway
2) The intrinsic or mitochondrial pathway
 Apoptosis is initiated by hormones, growth factors, heat, radiation, chemicals etc.

7. Caspase:-
 Caspase are cysteine dependent aspartate specific protease. They contain a key cysteine
residue in the catalytic site and selectively cleave proteins at sites just c- terminal to
aspartate residue.
 Caspase involved in apoptosis are classified in to two groups:-
1) Initiator caspase (caspases 2, 8, 9, 10)
2) executioner caspase (caspases 3, 6, 7)
 Procaspase are activated by dimerization which further activates executioner caspase.

8. Other important proteins:-
 BCL-2 family helps regulate the activation of procaspases.
 The family of protein consists of :-
Anti-apoptotic members – BCL-2 itself, BCL-X and BCL-B
Pro-apoptotic members – BAX, BAD, BIK
 The pro-apoptotic BCL-2 proteins consists of two subfamilies –
BH123 proteins -(BAX and BAK) promotes MOMP and release of cytochrome c.
BH3- only proteins – (BID, BIM, BIK, BAD, PUMA and NOXA) inhibition of of the anti-
apoptotic proteins and direct activation of the pro-apoptotic proteins.
 IAP inhibit caspases by promoting the degradation of active caspases.

9. The extrinsic pathway:-
 A number of extra cellular signal molecules is specialized to induce apoptosis. These extra
cellular signal molecules bind with cell surface receptors(death receptors).
 The intraction of FasL & FasR on the target cell triggers apoptosis. This intarction recruit
Fas-Assciated protein with Death Domain.
 FADD recruits procaspse-8 which I cleaved to generate active caspase-8. this complex is
called DISC (death inducing signal complex).
 In turn caspase-8 activates executioner caspase-3 or -7
 Which triggers apoptosis or cell death.

10. The intrinsic pathway:-
 It is induced by intracellular death signal. Mitochondria plays a central role by releasing
cytochrome c
 The events during the intrinsic apoptotic pathway:-
 Mitochondrial outer membrane permeabilization (MOMP)
 release of cytochrome c in the cytosol
 Cytochrome c binds to adaptor protein APAF-1
 Formation of apoptosome (heptameric complex) by hydrolysis of ATP into ADP
 Activation of procaspase-9 into caspase-9
 Activation of procaspase-3 into caspase-3
 Caspase-3 triggers apoptosis

11. Fig:- Molecular mechanism of apoptosis

12. Apoptosis and cancer:-
DNA damage & chromosome abnormalities
P53
cell cycle arrest apoptosis unlimited cell
proliferation
DNA repair Death & elimination
of damaged cells cancer
Loss of P53 function

13. Refrences :-
 https://www.annualreviews.org/doi/abs/10.1146/annurev.biochem.73.011303.07370.
 https://www.genome.gov/genetics-glossary/apoptosis.
 https://www.ewg.or.g/research/hallmarks-cancer/evading-apoptosis.