Porth's Essentials of Pathophysiology, 4e

7

Cell Structure and Function

C h a p t e r 1

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.

Cell membrane

Mitochondrion

Microtubule

Rough endoplasmic reticulum

Nucleus

Ribosomes

Microfilament

Intermediate filaments

FIGURE 1-7. Three-dimensional view of the network of microtubules, microfilaments, and intermediate filaments that supports the organelles within the cell cytoplasm.

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.

Made with