Concept 7.5: Programmed Cell Death Is a Necessary Process in Living Organisms

Cells die in one of two ways. The first type of cell death, necrosis, occurs when cells are damaged by mechanical means or toxins, or are starved of oxygen or nutrients. These cells often swell up and burst, releasing their contents into the extracellular environment. This process often results in inflammation (see Concept 39.1).

More typically, cell death is due to apoptosis (Greek, “falling apart”). Apoptosis is a genetically programmed series of events that result in cell death. Why would a cell initiate apoptosis, which is essentially cell suicide? In animals, there are two possible reasons:

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The events of apoptosis are similar in many organisms. The cell becomes detached from its neighbors, it hydrolyzes its DNA into small fragments, and forms membranous lobes, or “blebs,” that break up into cell fragments (FIGURE 7.15A). In a remarkable example of the economy of nature, the surrounding living cells usually ingest the remains of the dead cell by phagocytosis. The remains are digested in the lysosomes, and the digestion products are recycled.

Figure 7.15: Apoptosis: Programmed Cell Death (A) Many cells are programmed to “self-destruct” when they are no longer needed, or when they have lived long enough to accumulate a burden of DNA damage that might harm the organism. (B) Both external and internal signals stimulate caspases (or similar enzymes in plants), which break down specific cell constituents, resulting in apoptosis.

Apoptosis is also used by plant cells in an important defense mechanism called the hypersensitive response. Plants can protect themselves from disease by undergoing apoptosis at the site of infection by a fungus or bacterium. With no living tissue to grow in, the invading organism is not able to spread to other parts of the plant. Because of their rigid cell walls, plant cells do not form blebs the way animal cells do. Instead, they digest their own cell contents in the vacuole and then release the digested components into the vascular system.

Despite these differences between plant and animal cells, they share many of the signal transduction pathways that lead to apoptosis. Like the cell division cycle, programmed cell death is controlled by signals, which may come from inside or outside the cell. Internal signals may be linked to the age of the cell or the recognition of damaged DNA. External signals can be detected by receptors in the cell membrane, and in turn they activate signal transduction pathways. Both internal and external signals lead to the activation of a class of enzymes called caspases in animals or of a functionally similar class of enzymes in plants. These enzymes hydrolyze target proteins in a cascade of events. The cell dies as the caspases hydrolyze proteins of the nuclear envelope, nucleosomes, and cell membrane (FIGURE 7.15B).

APPLY THE CONCEPT: Programmed cell death is a necessary process in living organisms

The DNA content of an individual cell can be measured by applying a DNA-specific dye to the cell and then passing it through an instrument that measures the staining intensity. A new drug was tested on a population of rapidly dividing tumor cells, and the DNA contents of the treated cells were analyzed and compared with those of untreated cells:a

  1. Plot percentage of cells versus dye intensity for the untreated and treated cells.
  2. Explain the data for the untreated cells. Which cells are in G1? What do the data indicate about how much time cells spend in G1 relative to other phases?
  3. Explain the data for treated cells and compare them with untreated cells. At what stage of the cell cycle do you think the new drug acts?

a Author’s own, unpublished data.

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CHECKpoint CONCEPT 7.5

  • What are some differences between apoptosis and necrosis?
  • Give examples of situations in which apoptosis occurs in animals and in plants.
  • In the worm Caenorhabditis elegans the fertilized egg divides by mitosis to produce 1,090 somatic cells. But the adult worm has only 959 cells. What happens to the 131 other cells formed during worm embryo development? What might happen if the 131 cells did not undergo this process?

Question 7.2

How does infection with HPV result in uncontrolled cell reproduction?

ANSWER Human papillomavirus (HPV) stimulates the cell cycle when it infects tissues lining the cervix. It does this by “hijacking” the regulatory mechanisms that control the cell cycle (Concept 7.3). There are two types of proteins that regulate the cell cycle:

Most tumors are treated by surgery. But when a tumor has spread from its original site (a common occurrence, unfortunately), surgery does not cure it. Instead, drugs—chemotherapy—are used. Generally, these drugs stop cell division by targeting specific cell cycle events (Concepts 7.2 and 7.3). For example, some drugs block DNA replication (e.g., 5-fluorouracil); others damage DNA, stopping the cells at G2 (e.g., etoposide); and still others prevent the normal functioning of the mitotic spindle (e.g., paclitaxel). Many of these drugs do not kill the cell, but they cause the cell cycle to stop, and the damaged cell is stimulated to undergo apoptosis (Concept 7.5).

A major problem with these treatments is that they target normal cells as well as the tumor cells. They are toxic to tissues with large populations of normally dividing cells such as those in the intestine, skin, and bone marrow (producing blood cells). There is an ongoing search for better and more specific drugs. For example, a drug has been identified that affects the protein produced as a result of the translocation between chromosomes 9 and 22 (Concept 7.4). The drug is rather specific and has been very successful at treating leukemia caused by this translocation.

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In this chapter we examined the cell cycle and cell division by binary fission and mitosis. We have seen how the normal cell cycle is disrupted in cancer. We also examined meiosis and the production of haploid cells in sexual life cycles. In the coming chapters we will examine heredity, genes, and DNA. In Concept 8.1 we will discuss Gregor Mendel’s studies of heredity and how the enormous power of his discoveries founded the science of genetics.