These organelles are the power houses of the cell and contain the molecular machinery for the conversion of energy from the breakdown of glucose into adenosine triphosphate (ATP), the energy currency of the cell. The energy stored in the high energy phosphate bonds of ATP is then available to power cellular functions. Mitochondria are mostly protein, but some lipid, DNA and RNA are present. The unique structure of these organelles can be seen under the electron microscope. These generally spherical organelles have an outer membrane surrounding an inner membrane that folds (cristae) into a scaffolding for oxidative phosphorylation and electron transport enzymes. Most mitochondria have flat shelf-like cristae, but those in steroid secreting cells may have tubular cristae. The mitochondrial matrix contains the enzymes of the citric acid cycle, fatty acid oxidation and mitochondrial nucleic acids.
Mitochondrial DNA is double stranded and circular. Mitochondrial RNA comes in the three standard varieties; ribosomal, messenger and transfer, but each is specific to the mitochondria. Some protein synthesis occurs in the mitochondria on mitochondrial ribosomes that are different than cytoplasmic ribosomes. Other mitochondrial proteins are made on cytoplasmic ribosomes with a signal peptide that directs them to the mitochondria. The metabolic activity of the cell is related to the number of cristae and the number of mitochondria within a cell. Cells with large amounts of metabolic activity, such as heart muscle, have many well developed mitochondria. New mitochondria are formed from preexisting mitochondria when they grow and divide.
Ribosomes are small organelles composed of ribosomal RNA (rRNA) and 80 some different proteins. rRNA is synthesized in the nucleolus and the ribosomal subunits are assembled there from rRNA and imported cytoplasmic made proteins. Once assembled, the subunits pass through the nuclear pores to the cytoplasm where they take part in protein synthesis. Some ribosomes are free in the cytoplasm and can be recruited to a polyribosomal structure when a messenger RNA (mRNA) strand is to be translated into a cytoplasmic protein. Other ribosomes are attached to the endoplasmic reticulum where the protein is formed within the interior to the endoplasmic reticulum. These proteins are destined for secretion, storage or incorporation into membranes.
Within the cytoplasm of cells is a 3-dimensional maze of connecting and branching channels made by a continuous membrane. This is called the endoplasmic reticulum (ER). ER can be classified as rough ER when ribosomes are attached to the cytosolic side of the membrane or smooth ER when no ribosomes are present. Rough ER is prominent in cells that are making proteins for export such as digestive enzymes, hormones, structural proteins or antibodies. The main function of rough ER is the segregation of proteins destined for export from the cell or for intracellular use. Proteins are modified within the ER by the addition of carbohydrate, removal of a signal sequence and other post-translational modifications. Phospholipid synthesis and assembly of multichain proteins also occur there.
Smooth ER lacks attached ribosomes and often appears more tubular than rough ER. The two types of ER are continuous in some sections. Smooth ER confers on the cell the ability to perform a variety of specialized functions. It is necessary for steroid synthesis, metabolism and detoxification of substances in the liver, phospholipid synthesis, and excitation-contraction coupling in skeletal muscle.
The Golgi, a curved membrane stack resembling a stack of pancakes, finishes the post-transitional modifications, concentrates and packages proteins for export or storage. It also adds directions for the destination of the protein package. Proteins made within the rough ER bud off in vesicles and are transported to the Golgi where the vesicles fuse with the membrane and the components are further modified, concentrated and packaged by the time they bud off as vesicles on the opposite side of the Golgi. Therefore, the Golgi shows a polarity in that one side accepts incoming vesicles (convex or cis face) and the final product vesicles bud off the opposite side (concave or trans face). In fact, biochemical studies have shown that the enzymes present within the Golgi are different at different levels of the membrane stack.
Lysosomes are membrane bound vesicles (0.05 to 0.5 micron) containing more than 40 hydrolytic enzymes that can digest most biological macromolecules. These organelles are the sites of intracellular digestion that are more numerous in cells performing phagocytosis. The limiting membrane keeps the digestive enzymes separate from the cytoplasm. The most common lysosomal enzymes are acid phosphatase, ribonuclease, deoxyribonuclease, proteases, sulfatases, and lipases. The enzymes function optimally at pH 5 and are mostly inactive at the pH of the cytosol (7.2). This taken with the limiting membrane protects the cell from digesting itself. Lysosomal enzymes are synthesized on the rough ER, transferred to the Golgi for modification and packaging. The cellular machinery attaches a directional signal to the enzymes (mannose-6-phosphate) that allows the ER and Golgi to sort these proteins and, via a receptor mediated process, segregate them to forming lysosomes.
Primary lysosomes are small concentrated sacs of enzymes that are not digesting anything. Primary lysosomes fuse with a phagocytic vacuole to become secondary lysosomes or phagolysosomes where digestion begins. As the substances are digested the nutrients diffuse through the lysosomal membrane to the cytosol. Residual bodies are formed when indigestible things remain in the vacuoles. In cells with a long life span such as cardiac muscle cells, residual bodies are more numerous and are referred to lipofuscin or age pigment.
Lysosomes also participate in the turnover of cellular organelles. Cytoplasmic components become enclosed in a membrane that fuses with a primary lysosome to become an autophagosome. In bone, the lysosomal enzymes are released from osteoclasts to digest surrounding bone during the process of remodeling. Lysosomal enzymes are also involved in the process of inflammation.
These small (0.5 to 1.2 microns) containing oxidative enzymes. Peroxisomes contain amino oxidases, hydroxyacid oxidase and catalase. Catalase protects the cell from hydrogen peroxide damage. Enzymes involved in lipid metabolism are also found in peroxisomes. Peroxisomal enzymes are synthesized on the free cytosolic ribosomes with a signal sequence that directs them to peroxisomes. As enzymes are added the peroxisome grows and then splits into two smaller peroxisomes.
Secretory granules are found in cells that store products until stimulated to release them as in hormones, neurotransmitters or digestive enzymes. These membrane bound vesicles contain a concentrated from of the particular secretory product.
Within the cell is a complex network of filaments, anchor proteins, and protein motors that form a support and transportation scaffolding. This network provides shape to the cell and participates in cellular movement.
These variable length tubules have an outer diameter of 24 nm, a dense 5nm thick wall and central hollow core. Microtubule lengths are variable and can reach several micrometers. Microtubules are composed of repeating heterodimers of alpha and beta tubulin. The heterodimers, under the proper conditions, will spontaneously assemble into tubules in vitro or in vivo. Growth of existing microtubules is generally directional with one end growing faster than the other. Various microtubular organizing centers, such as basal bodies, centrioles and centromeres, direct the assembly and disassembly of microtubules. Microtubular life span is variable with some, as in those of the mitotic spindle, being transient, while others, such as those in cilia, being very stable. Some antimitotic alkaloids are useful as cancer chemotherapy agents. Taxol increases the formation of microtubules and stabilizes them so that there is no free tubulin for the formation of mitotic spindles. Vinblastine causes the disassembly of formed microtubules and causes the aggregation of crystaline tubulin. Because tumor cells multiply faster than normal cells they are more susceptible to antimitotic drugs. Some body systems are more affected than others based on their normal turnover rate. For instance, the cells of the gastrointestinal lining and blood forming system have rapid turnover rates and are therefore susceptible to the inhibition of mitosis caused by the chemotherapy agents.
Microtubules provide the necessary intracellular highway system for the movement of organelles and vesicles from one place to another. Molecular motors such as dynien and kinesin transport packages along this highway in an energy requiring process.
Actin and myosin are microfilament proteins responsible for contraction in muscle cells. All cells have actin in some form. Myosin in motile nonmuscle cells is present in unpolymerized form. It polymerizes only to participate in cell movement. In most cells, microfilaments form thin sheath just under the cell membrane that is associated with the cellular functions of endocytosis, exocytosis and cell movement. Microfilaments are involved with the movement of vesicles, granules and cytoplasmic organelles. In association with myosin, microfilaments form a "purse-string" ring that constricts and results in the cleavage of mitotic cells. Most of a nonmuscle cell's actin is soluble and microfilaments readily dissociate and reassemble under the influence of cellular calcium and cAMP (cyclic adenosine monophosphate) levels.
Intermediate filaments have an average diameter of about 10 nm and are made of several proteins dependent on the cell or tissue type. The proteins differ chemically and in their cellular roles.
1. Keratins are a family of proteins (40-68 kDa) found in most epithelial cells. The variety of keratins speaks to the variety of functions performed by skin, hair, nails in protection from abrasion and desiccation.
2. Vinmentin (56-58 kDa) filaments are found in cells of mesenchymal origin such as fibroblasts, macrophages, endothelial cells, and chondroblasts.
3. Desmin (53-55 kDa) is found in smooth muscle and in the Z lines of skeletal and cardiac muscle.
4. Glial Fibrillary Acidic Protein (51 kDa) is only found in glial cells (astrocytes).
5. Neurofilaments are found in most neurons and are composed of at least three polypeptides (68, 140 and 210 kDa).
6. Nuclear Laminins (65-75 kDa) are found in the nuclear lamina of cells.
These cylindrical organelles participate in cell division as microtubule organizing centers. They are in fact composed of tubulin in a characteristic arrangement of nine microtubular triplets. A single pair of centrioles oriented at a 90 degree angle to one another is found near the Golgi complex in non-dividing cells. Before cell division each centriole replicates itself. During mitosis a pair of centrioles moves to opposite poles of the cell to become organizing centers for the mitotic spindle.
Cilia and Flagella
Cilia and flagella have at their core a motile highly organized microtubular structure. Flagella usually exist as one process ranging in length from 100 to 200 microns. Sperm cells have a flagellum. Ciliated cells, such as those lining the respiratory tree, normally have numerous cilia ranging in length from 2 to 10 microns. Both types of cellular processes contain the same core organization of a 9 + 2 arrangement of microtubules within a cell membrane covering. This structure, called an axoneme, consists of 9 microtubular doublets surrounding an inner core of two sheathed microtubules. Adjacent doublets are linked to one another by protein bridges called nexins and to the central pair by radial spokes. The tubules of each peripheral pair are called subfibers A and B. Subfiber A is a complete microtubule containing 13 tubulin heterodimers in cross section, while subfiber B shares part of the wall of subfiber A and has only 10 or 11 heterodimers in cross section. Protein arms of the protein dynein extend from subfiber A. At the base of each cilia or flagella is a centriole-like structure called the basal body.
Cilia and flagella are motile structures. Movement is accomplished by the sliding of adjacent doublets over one another by an energy requiring process. The dynein arms have an ATPase activity and an affinity for tubulin. These arms are thought to bind and "walk" along the surface of the adjacent doublet.
The nucleus is a spherical, sometimes elongated structure that contains the genetic material, the DNA, of the cell. The highly organized chromatin within is enveloped by a nuclear membrane that contains numerous pores for the transport of large macromolecules and ribosomal subunits to the cytoplasm. The nuclear envelope is actually two parallel unit membranes with an intervening perinuclear space. Ribosomes are often attached to the outside membrane and it is sometimes continuous with the rough ER.
Chromatin consists of coiled DNA bound to basic proteins called histones and some less well defined non-histone proteins. The degree of coiling of the chromatin varies during cell activity. From microscopic examination two types of chromatin can be seen, dark, dense heterochromatin and light euchromatin. Basic proteins in highly coiled DNA stain darker. Therefore, cells with light nuclei are more active, i.e. their chromatin is uncoiled, than those with condensed, dark nuclei. Lightly coiled DNA facilitates transcription because there is more surface area available.
The basic structure of the chromatin is the nucleosome, which consists of a core of histones with 166 DNA base pairs wrapped around the core. Nucleosomes have an intervening 48 base pair linking segment between them.
This spherical structure within the nucleus is composed of DNA, RNA and protein. The DNA present is that which codes for rRNA, known as nucleolar organizers. Proteins synthesized in the cytoplasm enter through the nuclear pores and become associated with the newly made rRNA in the nucleolus. Afterwards the ribosomal subunits migrate to the cytoplasm. The nucleolus disappears during cell division but reappears in the final stage of mitosis.
Within the nucleus among the nucleosomes is a matrix composed of proteins, metabolites and ions. When all else is removed there remains a fibrillar nucleoskeleton than may provide a scaffold for the folded DNA. A fibrous lamina (80 to 300 nm thick) lies just under the nuclear envelope. This lamina dissociates just prior to mitosis due to the phosphorylation of the laminins. Post-mitotic laminin dephosphorylation results in reformation of the nuclear lamina.