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Apoptosis
Programmed cell death/ cell suicide, essential part of normal health and development
Post mitotic cells
Cells that never divide
Senescent cells
During aging cells lose the ability to divide, permanently stuck in G0 phase (can’t enter cell cycle)
M phase
Mitosis (nuclear division), cytokinesis (cytoplasmic division)
G1 phase
Cell undergoes protein synthesis (gene transcription & rna synthesis occurs), duplicate organelles. Cells highly metabolically active during this stage
S phase
Cell duplicates dna, extra copy of each chromosome is made, sister chromatids joined at the centromere
G2 phase
Rapid period of cell growth, cell checks dna to make sure it has been copied correctly (phase is not always necessary)
M phase
Fastest stage, nuclear envelope breaks down, mitotic spindle forms & chromosomes are separated
Cytokinesis
Cell splits in two
Stages within M phase
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
In metaphase…
Chromosomes align at the centre of the cell along the metaphase plate
Kinetochore
Attaches chromosomes to microtubules, leading to segregation of chromosomes
Hayflick limit
Most cells from multicellular organisms have a limited lifespan even when all nutrients are provided (lifespan of around 40-60 divisions)
G0 phase
Cells that are not actively dividing, when more cells are needed cells can leave G0 and enter G1 phase
What limits the number of times a cell divides
Telomere shortening following cell division
Why are tumour cells immortal
Can rebuild their telomeres using enzyme telomerase
HeLa cells
Isolated from Henrietta lacks 1951 from cervical tumour, cells could be cultured indefinitely, used to test first polio vaccine
Commitment points
Ensure correct functioning of cell cycle
Necrosis
Uncontrolled cell death associated with disease
Importance of apoptosis
Embryo development
Immune system
Homeostasis
Cancer
Pathways for triggering apoptosis
Receptor mediated - extrinsic
Mitochondria mediated - intrinsic
Intrinsic pathway
Activated via mitochondria by variety of cell stresses (free radical damage, dna damage, viral infection or loss of survival signals)
Caspases
Executioners of apoptosis
Initiator caspases
Activate other caspases
Effector caspases
Break down cellular components such as cytoskeleton & dna
Role of cytochrome c
Located in the inner mitochondrial membrane
How is apoptosis triggered
Pores form in outer mitochondrial membrane allowing release of cytochrome c into cytosol, cytochrome c binds to other cytosolic proteins forming multi protein complex - apoptosome
The formation of the apoptosome requires…
Cytochrome c, apaf 1, procaspase 9 and atp
Pro-apoptosis members of bcl2
Insert themselves into mitochondrial surface, promote formation of large pores in outer membrane (leads to release of cytochrome c)
Anti apoptotic members
exist in the mitochondrial outer membrane, block action of pro apoptotic members
Caspases
Responsible for destruction of the cell
Bcl2 proteins function
Act on mitochondria to regulate formation of pores in the outer mitochondrial membrane