C h a p t e r 1
Cell Structure and Function
7
proteins of the mitochondria and other proteins needed
to carry out cellular respiration.
Mitochondrial DNA is inherited matrilineally (i.e.,
from the mother) and provides a basis for familial lin-
eage studies. Mutations have been found in each of the
mitochondrial genes, and an understanding of the role
of mitochondrial DNA in certain diseases and of mech-
anisms to maintain the integrity of the mitochondrial
genome is beginning to emerge. Most tissues in the
body depend to some extent on oxidative metabolism
and can therefore be affected by mitochondrial DNA
mutations.
Mitochondria also function as key regulators of apop-
tosis or programmed cell death (discussed in Chapter 2).
The initiation of the mitochondrial pathway for apopto-
sis results from an increase in mitochondrial membrane
permeability and the subsequent release of proapoptotic
molecules into the cytoplasm. One of these proapoptotic
molecules, cytochrome c, is well known for its role in
cellular respiration. In the cytosol, cytochrome c binds
to a protein called the
apoptosis protease activating
factor-1
protein, initiating the molecular events involved
in the apoptosis cascade. Other apoptotic proteins also
enter the cytoplasm, where they bind to and neutralize
the various apoptotic inhibitors, whose normal func-
tion consists of blocking the apoptotic cascade. Both
the formation of reactive oxygen species (e.g., peroxide)
and the activation of the p53 tumor-suppressor gene by
DNA damage or other means initiate apoptotic signal-
ing through the mitochondria. Dysregulated apoptosis
(too little or too much) has been implicated in a wide
range of diseases, including cancer, in which there is an
inappropriately low rate of apoptosis, and neurodegen-
erative diseases, in which there is an increased or exces-
sive rate of apoptosis.
The Cytoskeleton
In addition to its organelles, the cytoplasm contains a
network of microtubules, microfilaments, and interme-
diate filaments (Fig. 1-7). Because they control cell shape
and movement, these structures are a major component
of the structural elements called the
cytoskeleton
.
Microtubules
Microtubules are slender and rigid tubular structures
composed of globular proteins called
tubulin
. Each
microtubule consists of parallel protofilaments, each
composed of
α
- and
β
-tubulin dimers. Microtubules
function in many ways, including the development and
maintenance of cell form; participation in intracellular
transport mechanisms, including axoplasmic trans-
port in neurons; and formation of the basic structure
for several complex cytoplasmic organelles, includ-
ing the cilia, flagella, and centrioles.
Cilia
and
flagella
are microtubule-filled cellular extensions extending
from the cell membrane that are capable of sweeping
movements. Cilia are found on the apical (luminal)
surfaces of many epithelial linings, including the nasal
sinuses and passages of the upper respiratory system.
Removal of mucus from the respiratory passages is
highly dependent on the proper functioning of the cilia.
Flagella form the tail-like structures that provide motil-
ity for sperm. Centrioles are small, barrel-shaped bod-
ies oriented at right angles to each other. In dividing
cells, the two cylindrical centrioles form the mitotic
spindle that aids in the separation and movement of the
chromosomes during cell division.
Abnormalities of the microtubules occur in a number
of pathologic states. These abnormalities may be mani-
fested by an abnormal appearance and function, aber-
rant movements of intracellular organelles, and defective
cell locomotion. Defective organization of the microtu-
bules can cause sterility by inhibiting sperm motility, as
well as defective motility of cilia in the epithelial lining
of the respiratory tract, resulting in chronic respiratory
tract infections. Proper functioning of the microtubules
is also essential for various stages of leukocyte migra-
tion. Drugs that bind to tubulin molecules and prevent
their assembly of microtubules (
colchicine
) are useful in
the treatment of gout, in which symptoms are due to
movement of leukocytes toward urate crystals in the tis-
sues. Since microtubules form the mitotic spindle, which
is essential for cell proliferation, drugs that bind micro-
tubules (e.g., vinca alkaloids) are useful in the treatment
of cancer.
Mitochondrion
Cell membrane
Rough
endoplasmic
reticulum
Nucleus
Microtubule
Microfilament
Intermediate
filaments
Ribosomes
FIGURE 1-7.
Three-dimensional view of the network of
microtubules, microfilaments, and intermediate filaments that
supports the organelles within the cell cytoplasm.
