3.3 Apoptosis

3.3

Apoptosis

KEY IDEAS

The normal functioning of an organism involves the process of interphase and the reproduction of cells through mitosis and cytokinesis. When a cell is damaged and cannot be repaired, or is not required anymore, its death needs to be regulated so that it doesn’t damage any other cells in the process. If a cell is exposed to toxins or extreme temperatures or is damaged, it can swell and eventually lyse, meaning the membrane breaks and the contents are released. This can cause the surrounding cells to become damaged and also die. This process of swelling and breaking apart is called necrosis. To prevent this from happening, cells need to have a safe, organised cell death pathway. Programmed cell death ( apoptosis ) is important when there is an excess of cells; for example, when an infection is under control and high levels of white blood cells are no longer needed, or when the body needs to remove a virusinfected cell. The signal that starts the process of apoptosis can come from an internal (intrinsic) or external (extrinsic) source (Figure 1).

Intrinsic pathway to apoptosis

intrinsic pathway The intrinsic pathway to cell death involves internal processes. These may be in response a biochemical to cell damage that is irreparable. pathway occurring completely within a cell that triggers Mitochondrial damage apoptosis Cytochrome c is a small protein found on the inner membrane of mitochondria, where it cytochrome c plays a part in aerobic cellular respiration. When a mitochondrion is damaged, cytochrome c a small protein on the leaks into the cytoplasm, where it can activate apoptosis. inner membrane of mitochondria, which is involved in the DNA damage electron transport A cell’s DNA is regularly checked by a multitude of repair enzymes. If the DNA is damaged,chain of aerobic cellular respiration the protein p53 attempts to repair the damage and blocks the cell cycle from progressing, giving the DNA more time to repair. If the DNA cannot be repaired, p53 initiates apoptosis in the cell by activating the mitochondria to release cytochrome c into the cytoplasm.

In this topic, you will learn that: ✚ apoptosis is a natural, regulated process of programmed cell death ✚ internal or external signals can lead a cell to apoptose. FIGURE 1 Apoptosis can be activated through an intrinsic or extrinsic pathway.

TNF-α Mitochondrion

Cytochrome c released

Intrinsic pathway

Extrinsic pathway Death receptor Caspases activated APOPTOSIS DRAFT ONLY - NOT FOR SALE

Extrinsic pathway to apoptosis

tumour necrosis factor-α (TNF-α)

Some cells in the immune system can release signalling molecules that cause other cells to apoptose. Tumour necrosis factor-α (TNF-α) is one of these signalling molecules released by white blood cells. Whereas other TNFs have roles in fighting disease and inflammation, a signalling molecule that has roles in TNF-α has been linked directly to apoptosis. It binds to a death receptor on the surface of inflammation and other cells and starts a series of internal chemical pathways that results in the activation of apoptosis p53 and ultimately leads to release of cytochrome c and apoptosis.

death receptor

a receptor on the surface of a cell that Stages of apoptosis initiates a cell the death of Once apoptosis has been initiated, the cell goes through a series of stages. • A series of enzymes called caspases are activated. These enzymes start breaking apart caspases the cytoskeleton of the cell. protease enzymes that are responsible • The cell starts shrinking. for many steps in the • The DNA is broken down. apoptosis pathway • The cell membrane forms small bulges called blebs . These contain the partly broken bleb down organelles of the cell. a bulge of cellular • The blebs become fully surrounded by the membrane and break off from the rest of the contents on the outside of an cell to form apoptotic bodies . apoptotic cell

apoptotic body

a bleb that has separated from a cell but is still enclosed in membrane Cell Apoptotic body formation Once all of the cell contents have separated into individual blebs, they are endocytosed by white blood cells in the immune system. If apoptosis is not controlled, excessive cell death can occur. Uncontrolled cell death (called necrosis) can cause toxic molecules to be released, and damage the surrounding healthy cells. A cell can limit its chances of apoptosis by producing inhibitors such as BCl-2 or decreasing the production of caspases.

Chromatin condensation Membrane blebbing

Nuclear collapse FIGURE 2 Apoptosis is a form of programmed cell death that allows a cell to safely form apoptotic bodies from blebs. FIGURE 3 This apoptotic cell is undergoing blebbing. DRAFT ONLY - NOT FOR SALE

CHALLENGE 3.3

Webbed fingers

Apoptosis plays a vital part in the development of an embryo (<11 weeks) and a foetus (>11 weeks). Five weeks after conception, the embryo begins to develop arms and legs. Tiny limb buds grow and elongate to form hand plates. At eight weeks, the cells between the fingers and toes apoptose, leaving five digits. Many genes are involved in this process. 1 Explain what could have occurred during development to result in the condition shown in Figure 5.

FIGURE 4 The hand plate of an embryo and the site of apoptosis to form five fingers FIGURE 5 This person has the condition of webbed fingers.

Describe and explain

1 Describe when a cell might undergo apoptosis. 2 Describe the stages of apoptosis. 3 Explain how caspases are involved in apoptosis.

Apply, analyse and compare

4 Compare the intrinsic and extrinsic pathways of apoptosis. 5 Compare necrosis and apoptosis.

Design and discuss 6 Research different outcomes that may occur when too much apoptosis happens in in the human body. 7 Discuss how apoptosis could play a role after the immune system has defeated a bacterial infection. CHECK YOUR LEARNING 3.3 DRAFT ONLY - NOT FOR SALE