1022-7954/04/4002- © 2004
Russian Journal of Genetics, Vol. 40, No. 2, 2004, pp. 99–113. Translated from Genetika, Vol. 40, No. 2, 2004, pp. 149–166.
Original Russian Text Copyright © 2004 by Popov, Korochkin.
Humankind has always been concerned with natural
physiological problems of death (apoptosis) and
immortality (we discussed the latter issue earlier ).
What is apoptosis? Elimination of unnecessary cells
is vitally important and commonly occurs during indi-
vidual development, particularly during embryogene-
sis, metamorphosis, renewal of cell composition in var-
ious tissues, and functioning of the immune system.
This elimination is carried out through apoptosis, a
phenomenon that is drawing increasing attention in
molecular genetics of development.
Apoptosis is a genetically programmed cell suicide.
This term is derived from the Greek
ing a plant shedding leaves. Apoptosis is involved in the
following processes: (1) form development; (2) precise
regulation of the number of cells constituting certain
cell assemblies; (3) removal of excessive of potentially
dangerous cells, e. g., lymphocytes of some types;
(4) tumor cells; and (5) virus-infected cells [2–4].
What are the differences of apoptosis from common
necrotic cell death?
Apoptosis should be distinguished from common
necrotic cell death. The latter, as a rule, is caused by
acute cell damage, which involves rapid swelling and
death of the cell. By contrast, apoptosis is characterized
by speciﬁc phenomenology:
1. Condensation of the cell nucleus and degradation
of nuclear DNA via endonuclear cleavage of chromo-
some DNA, which breaks ﬁrst into large (50–300 kb)
and then into very small fragments .
2. In the case of apoptosis, cell death is suicidal
because cells execute an internal program of their death
including activation of endogenous proteases, protein-
degrading enzymes . In view of this, apoptosis is
often referred to as programmed cell death (PCD).
3. PCD is regulated by intercellular relationships; as
a result, the organism can eliminate undesirable cells .
4. PCD is characterized by loss of the mitochondrial
function, which implies a signiﬁcant role of mitochon-
dria in apoptosis regulation. Nevertheless, the dying
cell maintains integrity of its plasmatic membrane .
5. Apoptosis-controlling genes have been identiﬁed
[3, 4]. For instance, early studied of apoptosis have
shown that drugs arresting protein synthesis prevent
apoptosis. Hence, programmed cell death requires syn-
thesis of speciﬁc proteins (in particular, the speciﬁc
protein annexin, whose presence is diagnostic for apo-
ptosis) and, consequently, depends on genes for these
proteins. However, in some cases these substances can
induce apoptosis, which testiﬁes to the constant pres-
ence of apoptosis effectors in mammalian cells. Inhibi-
tors of RNA or protein synthesis do not arrest apopto-
sis. Moreover, cells with nuclei removed by cytochala-
sin or centrifugation, all die showing characteristic
signs of PCD.
6. In view of these data, it is generally thought that
all genes required for apoptosis are constitutively
expressed in mammalian cells. The requirement for
synthesis of in RNA or proteins for induction of pro-
grammed cell death may reﬂect the requirement for
synthesis of molecules activating the already existing
PCD machinery rather than components producing cell
Apoptosis may appear as a result of a genetically
regulated program switched by speciﬁc death signals. A
universal signal has not been yet identiﬁed. Its stereo-
typical nature implies that a common evolutionarily
conserved pathway underlie many, if not all, cases of
apoptotic death. This view is conﬁrmed by the exist-
ence of a family of structurally related proteins regulat-
ing apoptotic responses of stimuli in various types of
cells [2, 4]. Recent years witnessed discovery of many
novel genes expressing not only proteins from the
BCL-2 family but also diverse proteins inhibiting or
Components of the BCL-2 protein have been exam-
Apoptosis: Genetically Programmed Cell Death
L. S. Popov
and L.I. Korochkin
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 117334 Russia
Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 117808 Russia
Received February 20, 2003; in ﬁnal form, August 21, 2003
—Extensively and successfully studied problems of programmed cell death are considered. Recent
evidence on apoptosis genes is presented, including the
family and other genes with similar functions. A
scheme of pathways of the main apoptosis mechanism is constructed. Examples of associations of apoptosis
and diseases are presented in a special section.