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Types of cell death

Two main ways in which cells can die:


1. Necrosis: (uncontrolled cell death). Associated with disease.
2. Apoptosis (programmed cell death or cell suicide). Apoptosis is an
essential part of normal health and development. In an average adult
between 50 and 70 billion cells die through apoptosis per day. In a year
your entire body weight of cells will have died through apoptosis.
Importance of apoptosis
1. Immune system – destroying self-reacting immune cells.
2. Immune system – destroying virus infected cells.
3. Homeostasis – as a counter-balance to cell division and removal of old or
damaged cells.
Cancer – radiotherapy and most chemotherapy drugs work by inducing
apoptosis. Many cancer cells have defects in the apoptosis pathways that make
them resistant to apoptosis.
How is apoptosis triggered?
Two main pathways for triggering apoptosis:
1. Receptor mediated (extrinsic pathway)
2. Mitochondria mediated (intrinsic pathway). The intrinsic pathway can be
activated by a variety of cell stresses such as free radical damage, DNA
damage, viral infection, or loss of survival signals.
Both pathways induce apoptosis by activating a class of proteases in the cell
called caspases.
Caspases - cysteine-aspartic proteases.
A family of 12 proteases that exist as inactive pro-enzymes in cells.
Following activation by cleavage they can activate other caspases in a cascade.
There are two types of apoptotic caspases:
1. Initiator caspases: activate other caspases.
2. Effector (executioner) caspases: break down cellular components such as
the cytoskeleton and DNA.
Activation of caspases is the point of no return in the process of apoptosis.
Role of mitochondria in apoptosis:
Cytochrome C is located in the inner mitochondrial membrane and is an
essential component of the electron transport chain.
In the intrinsic apoptosis pathway, pores form in the outer mitochondrial
membrane allowing release of cytochrome C into the cytosol. Since
cytochrome C is normally only found in the mitochondria, its release into the
cytosol acts as a trigger for apoptosis. Cytochrome C binds to other cytosolic
proteins to form a multi-protein complex called the apoptosome.
The formation of the apoptosome requires cytochrome C, a protein called
Apaf-1, pro-caspase 9 and ATP.
There are 7 molecules of each protein in the complete apoptosome with a
combined molecular weight of 700 KDa.
The end result is the cleavage and therefore activation of pro-caspase 9 into
active caspase 9, an initiator caspase.

What controls the release of cytochrome C from the mitochondria?


The Bcl-2 family of proteins is responsible for the regulation of cytochrome C
release from the mitochondria. There are around 20 members of the family
and consist of both pro-apoptotic and anti-apoptotic proteins. Their ability to
induce apoptosis depends on the balance between the two types.
The Bcl-2 family of proteins is responsible for the regulation of cytochrome C
release from the mitochondria. There are around 20 members of the family
and consist of both pro-apoptotic and anti-apoptotic proteins. Their ability to
induce apoptosis depends on the balance between the two types.
Anti-apoptotic members are thought to exist in the mitochondrial outer
membrane and act to block the action of the pro-apoptotic members.