• It is a genetically encoded and evolutionaryconserved form of cell death, in which anyharm done to the organism by this process isminimized.

• Apoptosis may occur during normalphysiological condition, for example, duringembryonic development.

• In contrast, Necrosis is a form of energyindependent cell death that results from acutetissue injury or any disease.

Cell death by Suicide(Apoptosis)-Internal signals

-External signals

Cell death by injury(Necrosis)-Mechanical damage

-Exposure to toxic chemicals

Because-

• Apoptosis is needed for proper development for

examples: The formation of the fingers and toes

of the fetus, the resorption of tadpole tail at the

time of metamorphosis.

• Apoptosis is needed to destroy malfunctioned

cells. For example , Cells infected with viruses,

Cells of the immune system ,Cells with DNA

damage, Cancer cells etc.

mermbane blebbing & changes

mitochondrial leakageorganelle reduction

cell shrinkage

ncluear fragmentationchromatin condensation

• Broadly of two Types-

-Capase Independent(Less common)

- Caspase Dependent(More Common)

• Caspase Dependent Pathways

- Extrinsic or Death Receptor Pathway

- Intrinsic or Mitochondrial Pathway

- Perforin/Granzyme Pathway(Granzyme B

mediated Apoptosis)

Schematic representation of three types of pathways of Apoptosis

• The cell cycle is a set of events responsible forcell duplication.

• The phases of the normal cell cycle are G1 to S,S to G2 and ultimately G2 to M phase.

• When the cell undergoes differentiation, itexits from the G1 phase of the cell cycle toenter into quiescent state referred to as G0.

Schematic representation of Cell cycle regulation

• The timing and cell cycle events are monitoredduring cell cycle checkpoints that occur at the G1/Sphase boundary, in S phase and G2/M phases.

• Cell cycle progression can be blocked at thesecheckpoints in response to the status, for examplegrowth arrest can be induced when DNA damage isdetected or when chromosomes are misaligned onthe mitotic spindle.

• The cell cycle control is based on protein families: thecyclin and the cyclin dependent kinase (Cdks).

Cell Cycle Regulation: Cyclin and Cyclin dependent kinase

• It is involved in severaldifferent aspects of cell cyclearrest, apoptosis, control ofgenome integrity and DNArepair.

• It regulates a variety ofprocesses by transactivatinggenes that are involved indifferent cellular functions.

• p53 regulates the expressionof several proteins known toinfluence the apoptoticprocess.

• Bcl2 and Bax have opposingeffects on cell death: Bcl2inhibits or delays cell deathand Bax accelerates apoptosis. p53 pathway in Apoptosis

• Important in normal physiology / development– Development: Immune systems maturation,

Morphogenesis, Neural development

– Adult: Immune privilege, DNA Damage and wound repair.

• Excess apoptosis– Neurodegenerative diseases

• Deficient apoptosis– Cancer

– Autoimmunity

Apoptosis involves a cascade of complex eventswhich include the delivery of external signalsthrough defined receptor complexes, the wellregulated expression of a no. of genes, and theexecution of apoptosis by proteases andendonucleases. The regulation of cellproliferation and cell death can share commonmolecules in multicellular organisms. The cellhas integrated control of two antagonisticprocesses- cell proliferation and cell death at cellcycle checkpoints.

• Extrinsic and Intrinsic Apoptosis signal Pathway Review, Zhao Hongmei, Chapter 1

• Functional Significance of the perforin/Granzyme cell Death Pathway, Joseph A. Trapaniand Mark J. Smyth, Vol 2, October 2002

• Apoptosis: Molecular Mechanism, Fatima Cairrao, Pedro M Domingos, Encyclopedia ofLife Sciences, 2010

• Yun-Ji Lim, Ji-Ae Choi, Hong-Hee Choi, etal. Endoplasmic Reticulum Stress Pathway-Mediated Apoptosis in Macrophages Contributes to the Survival of Mycobacteriumtuberculosis. Plosone. 2011, 6(12): e28531

• Zhou J, Lu GD, Ong CS, et al. Andrographolide sensitizes cancer cells to TRAIL inducedapoptosis via p53-mediated death receptor 4 up-regulation. Mol Cancer Ther.2008,7(7):2170-2180.

• Chao DT and Korsmeyer SJ (1998) BCL-2 family: regulators of cell death. Annual Reviewof Immunology 16: 395-419.

• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885741/