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Mitochondria

Mitochondria

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Figure 1-1-7.The Peroxisome

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Figure 1-1-7.The Peroxisome

Mitochondria

Mitochondria have two membranes. They are about 0.5 fxm in width and vary in length from 1 to 10 |xm (Figure 1-1-8). They synthesize adenosine triphosphate (ATP), contain their own double-stranded circular DNA, and make some of their own proteins. Mitochondria have several compartments.

Outer membrane

The outer membrane is smooth, continuous, and highly permeable. It contains an abundance of porin, an integral membrane protein that forms channels in the outer membrane through which molecules of less than 10 kD can pass.

Inner membrane

The inner membrane is impermeable to most small ions (Na+, K+, H+) and small molecules (ATP, adenosine diphosphate, pyruvate). The impermeability is likely related to the high content of the lipid cardiolipin.

• The inner membrane has numerous infoldings, called cristae. The cristae greatly increase the total surface area. They contain the enzymes for electron transport and oxidative phosphorylation.

• The number of mitochondria and the number of cristae per mitochondrion are proportional to the metabolic activity of the cells in which they reside.

Intermembrane compartment

The intermembrane compartment is the space between the inner and outer membranes. It contains enzymes that use ATP to phospborylate other nucleotides (creatine phosphokinase and adenylate kinase).

Matrix

The matrix is enclosed by the inner membrane and contains:

• Dehydrogenases—oxidize many of the substrates in the cell (pyruvate, amino acids, fatty acids), generating reduced nicotinamide adenine dinucleotide (NADH) and reduced flavin adenine dinucleotide (FADH2) for use by the electron transport chain and energy generation.

• A double-stranded circular DNA genome—encodes a few of the mitochondrial proteins. Mitochondrial DNA is always inherited from the mother, resulting in the maternal transmission of diseases of energy metabolism.

■ RNA, proteins, and ribosomes—although there is some protein synthesis, most mitochondrial proteins are synthesized in the cytoplasm and are transferred into the mitochondria.

■ Intramitochondrial granules—contain calcium and magnesium. Their function is not known, but it is believed that they may represent a storage site for calcium.

Cristae

Cristae

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Figure 1-1-8. Mitochondria

Copyright 2000 Gold Standard Multimedia, Inc. All rights reserved.

Figure 1-1-8. Mitochondria

Cytoskeleton

The cytoskeleton provides a supportive network of tubules and filaments in the cytoplasm of eukaryotic cells. It is composed of microtubules, intermediate filaments, and microfilaments.

Microtubules

Microtubules are polymers of tubulin that undergo rapid assembly and disassembly. They are found in the cytoplasmic matrix of all eukaryotic cells.

Cell Components

Tubulin

The major component of microtubules is tubulin, a protein dimer composed of two different polypeptides, a-tubulin and (3-tubulin.

Polymerization of tubulin to form microtubules is accomplished by microtubule organizing centers and two types of accessory proteins, tau proteins and microtubule-associated proteins. Microtubules grow from the organizing centers. Calcium ions can block or reverse polymerization.

Microtubules play a role in:

• Chromosomal movement during meiosis and mitosis. Microtubule assembly is an important event in spindle formation.

■ Intracellular vesicle and organelle transport. Two specific micro tubule-dependent ATPases, kinesin and dynein, are involved in generating the force that drives transport, with the micro tubular structure playing a more passive role in intracellular transport.

• Ciliary and flagellar movement.

Intermediate filaments

Intermediate filaments are intermediate in thickness (10-nm diameter) between microtubules and microfilaments. They function primarily in structural roles and contain several types of tissue-specific proteins'.

• Cytokeratins—found in epithelial tissue

• Desmin—found in smooth muscle; Z disks of skeletal and cardiac muscle

• Vimentin—found in cells of mesenchymal origin (endothelial cells, fibroblasts, chon-droblasts, vascular smooth muscle)

• Neurofilaments—found in neurons

• Glial fibrillary acidic protein (GFA)—found in astrocytes

Microfilaments

Microfilaments have a diameter of 6 nm and are composed of actin. Each actin filament (F-actin) consists of two strands of actin twisted into a helical pattern with 13.5 molecules of globular actin (G-actin) per turn of the helix.

Two types of movement are associated with microfilaments:

• Local movement takes advantage of the polymerization and depolymerization properties of microfilaments.

• Sliding filament movement is generated by the interaction of actin filaments with myosin filaments.

Clinical Correlate

Ch^diak-Higashi syndrome is characterized by a defect in microtubule polymerization. This leads to defects in cytoplasmic granules including:

• Delayed fusion of phagosomes with lysosomes in leukocytes, thus preventing phagocytosis of bacteria.

• Increased fusion of melanosomes in melanocytes, leading to albinism.

■ Granular defects in natural killer cells and platelets.

Clinical Correlate

Actin-binding drugs (e.g., cytochalasin B) can interfere with the polymerization-depolymerization cycle of microfilaments. Processes such as endocytosis, phagocytosis, cytokinesis, and cytoplasmic and amoeboid movements are all inhibited by cytochalasin B.

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