Mitochondria (Gr. mitos, thread, + chondros, granule) are spherical or filamentous organelles 0.5–1 m wide that can attain a length of up to 10 m (Figure 2–11). They tend to accumulate in parts of the cytoplasm at which the utilization of energy is more intense, such as the apical ends of ciliated cells (Figure 17–3), in the middle piece of spermatozoa (Figure 21–10), or at the base of ion-transferring cells (Figure 4–25).
Photomicrograph of the stomach inner covering. The large cells show many round and elongated mitochondria in the cytoplasm. The central nuclei are also clearly seen. High magnification.
These organelles transform the chemical energy of the metabolites present in cytoplasm into energy that is easily accessible to the cell. About 50% of this energy is stored as high-energy phosphate bonds in ATP molecules, and the remaining 50% is dissipated as heat used to maintain body temperature. Through the activity of the enzyme ATPase, ATP promptly releases energy when required by the cell to perform any type of work, whether it is osmotic, mechanical, electrical, or chemical.
Mitochondria have a characteristic structure under the electron microscope (Figures 2–12 and 2–13A). They are composed of an outer and an inner mitochondrial membrane; the inner membrane projects folds, termed cristae, into the interior of the mitochondrion. These membranes enclose two compartments. The compartment located between the two membranes is termed the intermembrane space. The inner membrane encloses the other compartment—the intercristae, or matrix, space. Compared with other cell membranes, mitochondrial membranes contain a large number of protein molecules. Most mitochondria have flat, shelflike cristae in their interiors (Figures 2–12 and 2–13A), whereas cells that secrete steroids (eg, adrenal gland; see Chapter 4: Epithelial Tissue) frequently contain tubular cristae (Figure 4–36). The cristae increase the internal surface area of mitochondria and contain enzymes and other components of oxidative phosphorylation and electron transport systems. The adenosine diphosphate (ADP) to ATP phosphorylating system is localized in globular structures connected to the inner membrane by cylindrical stalks (Figure 2–12). The globular structures are a complex of proteins with ATP synthetase activity that, in the presence of ADP plus inorganic phosphate and energy, forms ATP. The chemiosmotic theory suggests that ATP synthesis occurs at the expense of a flow of protons across this globular unit (Figure 2–14).
Three-dimensional representation of a mitochondrion with its cristae penetrating the matrix space. Note that two membranes delimiting an intermembrane space form the wall of the mitochondrion. The cristae are covered with globular units that participate in the formation of ATP.
Structural lability of mitochondria. A: Electron micrograph of a section of rat pancreas. A mitochondrion with its membranes, cristae (C), and matrix (M) is seen in the center. Numerous flattened cisternae of rough endoplasmic reticulum with ribosomes on their cytoplasmic surfaces are also visible. x50,000. B: Electron micrograph of striated muscle from a patient with mitochondrial myopathy. The mitochondria (arrows) are profoundly modified, showing marked swelling of the matrix.
The chemiosmotic theory of mitochondrial energy transduction. Middle: The flux of protons is directed from the matrix to the intermembranous space promoted at the expense of energy derived from the electron transport system in the inner membrane. Left: Half the energy derived from proton reflux produces ATP; the remaining energy produces heat. Right: The protein thermogenin, present in multilocular adipose tissue, forms a shunt for reflux of protons. This reflux, which dissipates energy as heat, does not produce ATP (see Chapter 6: Adipose Tissue).
The number of mitochondria and the number of cristae in each mitochondrion are related to the energetic activity of the cells in which they reside. Thus, cells with a high-energy metabolism (eg, cardiac muscle, cells of some kidney tubules) have abundant mitochondria with a large number of closely packed cristae, whereas cells with a low-energy metabolism have few mitochondria with short cristae.
Between the cristae is an amorphous matrix, rich in protein and containing circular molecules of DNA and the three varieties of RNA. In a great number of cell types, the mitochondrial matrix also exhibits rounded electron-dense granules rich in Ca2+. Although the function of this cation in mitochondria is not completely understood, it may be important in regulating the activity of some mitochondrial enzymes; another functional role is related to the necessity of keeping the cytosolic concentration of Ca2+ low. Mitochondria will pump in Ca2+ when its concentration in the cytosol is high. Enzymes for the citric acid (Krebs) cycle and fatty acid -oxidation are found to reside within the matrix space.
The DNA isolated from the mitochondrial matrix is double stranded and has a circular structure, very similar to that of bacterial chromosomes. These strands are synthesized within the mitochondrion; their duplication is independent of nuclear DNA replication. Mitochondria contain the three types of RNA: ribosomal RNA (rRNA), messenger RNA (mRNA), and transfer RNA (tRNA). Mitochondrial ribosomes are smaller than cytosolic ribosomes and are comparable to bacterial ribosomes. Protein synthesis occurs in mitochondria, but because of the reduced amount of mitochondrial DNA, only a small proportion of the mitochondrial proteins is produced locally. Most are encoded by nuclear DNA and synthesized in polyribosomes located in the cytosol. These proteins have a small amino acid sequence that is a signal for their mitochondrial destination, and they are transported into mitochondria by an energy-requiring mechanism.
The initial degradation of carbohydrates and fats is carried out in the cytoplasmic matrix. The metabolic end product of these extramitochondrial metabolic pathways is acetyl coenzyme A, which then enters mitochondria. Within mitochondria, acetyl coenzyme A combines with oxaloacetate to form citric acid. Within the citric acid cycle, several reactions of decarboxylation produce CO2, and specific reactions catalyzed by dehydrogenase result in the removal of four pairs of H+ ions. The H+ ions ultimately react with oxygen to form H2O. Through the action of cytochromes a, b, and c, coenzyme Q, and cytochrome oxidase, the electron transport system, located in the inner mitochondrial membrane, releases energy that is captured at three points of this system through the formation of ATP from ADP and inorganic phosphate. Under aerobic conditions, the combined activity of extramitochondrial glycolysis and the citric acid cycle as well as the electron transport system gives rise to 36 molecules of ATP per molecule of glucose. This is 18 times the energy obtainable under anaerobic circumstances, when only the glycolytic pathway can be used.
In the process of mitosis, each daughter cell receives approximately half the mitochondria originally present in the parent cell. New mitochondria originate from preexisting mitochondria by growth and subsequent division (fission) of the organelle itself.
The fact that mitochondria have some characteristics in common with bacteria has led to the hypothesis that mitochondria originated from an ancestral aerobic prokaryote that adapted to an endosymbiotic (intracellular symbiosis) life within a eukaryotic host cell.
Several diseases of mitochondrial deficiency have been described, and most of them are characterized by muscular dysfunction. Because of their high-energy metabolism, skeletal muscle fibers are very sensitive to mitochondrial defects. DNA mutations or defects that can occur in the mitochondria or the cell nucleus cause mitocondria diseases. Mitochondrial inheritance is maternal, because few, if any, mitochondria from the sperm nucleus remain in the cytoplasm of the zygote. In the case of nuclear DNA defects, inheritance may be from either parent or both parents. Generally, in these diseases the mitochondria show morphological changes (Figure 2–13B).
|Afzelius BA, Eliasson R: Flagellar mutants in man: on the heterogeneity of the immotile-cilia syndrome. J Ultrastruct Res 1979;69:43. [PMID: 501788] |
|Aridor M, Balch WE: Integration of endoplasmic reticulum signaling in health and disease. Nat Med 1999;5:745. [PMID: 10395318] |
|Barrit GJ: Communication Within Animal Cells. Oxford University Press, 1992. |
|Becker WM et al: The World of the Cell, 4th ed. Benjamin/Cummings, 2000. |
|Bretscher MS: The molecules of the cell membrane. Sci Am 1985;253:100. [PMID: 2416050] |
|Brinkley BR: Microtubule organizing centers. Annu Rev Cell Biol 1985;1:145. [PMID: 3916316] |
|Brown MS et al: Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell 1983;32:663. [PMID: 6299572] |
|Cooper GM: The Cell: A Molecular Approach. ASM Press/Sinauer Associates, Inc., 1997. |
|DeDuve C: A Guided Tour of the Living Cell. Freeman, 1984. |
|DeDuve C: Microbodies in the living cell. Sci Am 1983;248:74. |
|Dustin P: Microtubules, 2nd ed. Springer-Verlag, 1984. |
|Farquhar MG: Progress in unraveling pathways of Golgi traffic. Annu Rev Cell Biol 1985;1:447. [PMID: 3916320] |
|Fawcett D: The Cell, 2nd ed. Saunders, 1981. |
|Krstíc RV: Ultrastructure of the Mammalian Cell. Springer-Verlag, 1979. |
|Mitchison TJ, Cramer LP: Actin-based cell motility and cell locomotion. Cell 1996;84:371. [PMID: 8608590] |
|Osborn M, Weber K: Intermediate filaments: cell-type-specific markers in differentiation and pathology. Cell 1982;31:303. [PMID: 6891619] |
|Pfeffer SR, Rothman JE: Biosynthetic protein transport and sorting in the endoplasmic reticulum. Annu Rev Biochem 1987;56:829. [PMID: 3304148] |
|Rothman J: The compartmental organization of the Golgi apparatus. Sci Am 1985;253:74. [PMID: 3929377] |
|Simons K, Ikonen E: How cells handle cholesterol. Science 2000;290:1721. [PMID: 11099405] |
|Tzagoloff A: Mitochondria. Plenum, 1982. |
|Weber K, Osborn M: The molecules of the cell matrix. Sci Am 1985;253:110. [PMID: 4071030]|