dramatically, display membrane blebbing and DNA condensation, and are
subsequently digested by neighboring cells.
Apoptosis, in its narrowest interpretation as physiologically intended or
‘programmed cell death’—a term often used interchangeably for apoptosis—plays
an important role in embryonic development and in tissue homeostasis. But apoptosis
is also induced when the cell experiences accidents such as DNA damage. The
difference from ‘programmed cell death’ is therefore that the triggering signal is not
genetically encoded. Specifically, apoptosis activation can be interpreted in many
cases as an altruistic behavior of the cell to benefit the organism as a whole; an example
would be cell death induced in virus-infected cells or in cells that are in cancer
progression. The multitude of different instances of apoptosis induction is reflected
by the vast array of proapoptotic stimuli mentioned above. While the causes might
be different, ‘programmed cell death’ and accidental apoptosis are in most cases
mediated by a similar—or at least an overlapping—group of genes, many of which
come in gene families (Chapter 5).
As versatile as this program is, it is no surprise that many diseases can arise when
apoptosis fails (Thompson, 1995). Cancer is fostered if apoptosis is repressed,
allowing unrestrained proliferation; autoimmune diseases can arise if autoreactive
immune cells fail to die and attack the organism. However, degenerative diseases can
originate if too much apoptosis is initiated. This is especially serious for cells, such as
neurons, that do not renew themselves. While the above picture reflects the basic
understanding of apoptosis, it has been modified and rendered more precise in recent
years: Distinct signal transduction pathways have been elucidated that decide when
caspases are activated: the so-called extrinsic pathway (Green, 1998) is initiated by
receptors sitting on the cytoplasmic membrane (Chapter 1). The ‘intrinsic’ pathway
is activated within the cell and involves mitochondria as important organelles, both
as cell-death sensors and for the amplification of the proapoptotic signal (Chapter 7).
The involvement of such formerly inconspicuous cell compartments led to
speculation that every organelle has its own sensor for apoptosis. The endoplasmic
reticulum (ER) is meanwhile an established organelle in cell death that harbors
important cell-death regulators, some of which are conserved in evolution
(Chapter 6). The phylogenetic origin of apoptosis is attested by the finding that even
primitive life forms contain genes of apoptosis. Therefore, systems for the study of
apoptosis range from single-celled yeast (Chapter 8) to simple Metazoa (Chapter 9),
mammalian cell cultures (Chapter 12), and classical genetic systems such as those of
C. elegans (Chapter 10) and Drosophila (Chapter 11).
This book is subdivided into three main sections, the first of which starts with the
description of several genes regulating apoptosis to give the reader a basic
understanding of the signaling molecules involved. The narrative then progresses to
more complex cellular processes that involve whole organelles in apoptosis (the second
section). The third and final section is devoted to organisms that are used to study
the biology of apoptosis. It is concluded by a perspective on the subject of caspase-
independent cell death (Chapter 13), which could well be the topic of the next
paradigm-shift in apoptosis research, and which reminds us how much this is a work
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