Pedia News

The Cytoplasm and Its Organelles


The Cytoplasm and Its Organelles
The cytoplasm surrounds the nucleus, and it is in the cytoplasm that the work of the cell takes place. Cytoplasm is essentially a colloidal solution that contains water, electrolytes, suspended proteins, neutral fats, and glycogen molecules. Although not contributing to the cell’s function, pigments may also accumulate in the cytoplasm. Some pigments, such as melanin, which gives skin its color, are normal constituents of the cell. Bilirubin is a normal major pigment of bile; its excess accumulation in cells is evidenced clinically by a yellowish discoloration of the skin and sclera, a condition called jaundice.

Embedded in the cytoplasm are various organelles, which function as the organs of the cell. These organelles include the ribosomes, ER, Golgi complex, mitochondria, and lysosomes.

Ribosomes
The ribosomes serve as sites of protein synthesis in the cell. They are small particles of nucleoproteins (rRNA and proteins) that are held together by a strand of mRNA to form polyribosomes (also called polysomes). Polyribosomes exist as isolated clusters of free ribosomes within the cytoplasm (Fig. 4.2) or attached to the membrane of the ER. Whereas free ribosomes are involved in the synthesis of proteins, mainly enzymes that aid in the control of cell function, those attached to the ER translate mRNAs that code for proteins secreted from the cell or stored within the cell (e.g., granules in white blood cells).
Endoplasmic reticulum and ribosomes

Endoplasmic Reticulum
The ER is an extensive system of paired membranes and flat vesicles that connect various parts of the inner cell (see Fig. 4.2). Between the paired ER membranes is a fluid-filled space called the matrix. The matrix connects the space between the two membranes of the nuclear envelope, the cell membrane, and various cytoplasmic organelles. It functions as a tubular communication system for transporting various substances from one part of the cell to another. A large surface area and multiple enzyme systems attached to the ER membranes also provide the machinery for a major share of the cell’s metabolic functions.
Two forms of ER exist in cells—rough and smooth. Rough ER is studded with ribosomes attached to specific binding sites on the membrane. Proteins produced by the rough ER are usually destined to become components of lysosomes or other organelles, incorporated into cell membranes, or leave the cell as a secretory protein. The rough ER segregates these proteins from other components of the cytoplasm and modifies their structure for a specific function. For example, the synthesis of both digestive enzymes by pancreatic acinar cells and plasma proteins by liver cells takes place in the rough ER. All cells require a rough ER for the synthesis of lysosomal enzymes.
The smooth ER is free of ribosomes and is continuous with the rough ER. It does not participate in protein synthesis; instead, its enzymes are involved in the synthesis of lipid molecules, regulation of intracellular calcium, and metabolism and detoxification of certain hormones and drugs. It is the site of lipid, lipoprotein, and steroid hormone synthesis. The sarcoplasmic reticulum of skeletal and cardiac muscle cells is a form of smooth ER. Calcium ions needed for muscle contraction are stored and released from cisternae of the sarcoplasmic reticulum. The smooth ER of the liver is involved in glycogen storage and metabolism of lipid-soluble drugs.
The processing ability of the ER is not unlimited. If proteins accumulate in the ER faster than they can be processed, the cell is said to experience “ER stress,” and signaling mechanisms kick in to slow protein production and restore homeostasis. If these homeostatic responses fail, cell death (apoptosis) can result. Defects in the response to ER stress can cause inflammation and even cell death. They have been implicated in inflammatory bowel disease, a genetic form of diabetes mellitus, and a disorder of skeletal muscle known as myositis, as well as many other diseases.

Golgi Complex
The Golgi apparatus, sometimes called the Golgi complex, consists of four or more stacks of thin, flattened vesicles or sacs (see Fig. 4.3). These Golgi bodies are found near the nucleus and function in association with the ER. Substances produced in the ER are carried to the Golgi complex in small, membrane-covered transfer vesicles. Many cells synthesize proteins that are larger than the active product. The Golgi complex modifies these substances and packages them into secretory granules or vesicles. Insulin, for example, is synthesized as a large, inactive proinsulin molecule that is cut apart to produce a smaller, active insulin molecule within the Golgi complex of the beta cells in the pancreas. In addition to producing secretory granules, the Golgi complex is thought to produce large carbohydrate molecules that combine with proteins produced in the rough ER to form glycoproteins. Recent data suggest that the Golgi apparatus has yet another function: it can receive proteins and other substances from the cell surface by a retrograde transport mechanism. Several bacterial toxins, such as Shiga and cholera toxins, and plant toxins, such as ricin, that have cytoplasmic targets have exploited this retrograde pathway.
Golgi apparatus—Vesicles containing proteins come from the rough ER and merge with the cistern of the Golgi apparatus.

Lysosomes and Peroxisomes
Lysosomes can be viewed as the digestive system  of  the cell. These small, membrane-enclosed sacs contain powerful hydrolytic enzymes. These enzymes can break down excess and worn-out cell parts as well as foreign substances that are taken into the cell. All of the lysosomal enzymes are acid hydrolases, which means they require an acidic environment. The lysosomes provide this environment by maintaining a pH of approximately 5 in their interior. The pH of the cytoplasm, which is approximately 7.2, serves to protect other cellular structures from this acidity. Primary lysosomes are membrane-bound intracellular organelles that contain a variety of hydro- lytic enzymes that have not yet entered the digestive process. They receive their enzymes as well as their membranes from the Golgi apparatus. Primary lysosomes become secondary lysosomes after they fuse with membrane-bound vacuoles that contain material to be digested. Lysosomes break down phagocytosed material by either heterophagy or autophagy (Fig. 4.4).
The processes of autophagy and heterophagy, showing the primary and secondary lysosomes, residual bodies, extrusion of residual body contents from the cell, and lipofuscin-containing residual bodies.

Heterophagy refers to digestion of an exogenous substance phagocytosed from the cell’s external environment. An infolding of the cell membrane takes external materials into the cell to form a surrounding phagocytic vesicle, or phagosome. Primary lysosomes then fuse with phagosomes to form secondary lysosomes. Heterophagocytosis is most common in phagocytic white blood cells such as neutrophils and macrophages. Autophagy involves the segregation and disposal of damaged cellular organelles, such as mitochondria or ER, which the lysosomes must remove if the cell’s normal function is to continue. Autophagocytosis is most pronounced in cells undergoing atrophy. Although enzymes in the secondary lysosomes can break down most proteins,  carbohydrates, and lipids to their basic constituents, some materials remain undigested. These undigested materials may remain in the cytoplasm as residual bodies or are extruded from the cell by exocytosis. In some long-lived cells, such as neurons and heart muscle cells, large quantities of residual bodies accumulate as lipofuscin granules or age pigment. Other indigestible pigments, such as inhaled carbon particles and tattoo pigments, also accumulate and may persist in residual bodies for decades.
Lysosomes play an important role in the normal metabolism of certain substances in the body. In some inherited diseases known as lysosomal storage diseases, a specific lysosomal enzyme is absent or inactive, in which case the digestion of certain cellular substances (e.g., glucocerebrosides, gangliosides, sphingomyelin) does not occur.7 As a result, these substances accumulate in the cell. In Tay-Sachs disease, an autosomal recessive disorder, hexosaminidase A, which is the lysosomal enzyme needed for degrading the GM  ganglioside found in nerve cell membranes, is deficient. Although GM ganglioside accumulates in many tissues, such as the heart, liver, and spleen, its accumulation in the nervous system and retina of the eye causes the most damage.7 There are multiple lysosome storage diseases, and new guidelines are being developed by the American College of Medical Genetics regarding diagnostic criteria and management for Fabry, Gaucher, and Niemann-Pick A/B disease; glycogen storage disease type II; globoid cell leukodystrophy; metachromatic leukodystrophy; and mucopolysaccharidoses types.
Smaller than lysosomes, spherical membrane-bound organelles called peroxisomes contain a special enzyme that degrades peroxides (e.g., hydrogen peroxide). Unlike lysosomes, peroxisomes are not formed by the Golgi apparatus. Peroxisomes are self-replicating like mitochondria and are initially formed by proteins produced by free ribosomes.
Peroxisomes function in the control of free radicals. Unless degraded, these highly unstable chemical compounds would otherwise damage other cytoplasmic molecules. For example, catalase degrades toxic hydrogen peroxide molecules to water. Peroxisomes also contain the enzymes needed for breaking down very–long-chain fatty acids, which mitochondrial enzymes ineffectively degrade.  In liver cells, peroxisomal enzymes are involved in the formation of the bile acids.

Proteasomes
Three major cellular mechanisms are involved in the break- down of proteins, or proteolysis. One of these is by the previously mentioned endosomal–lysosomal degradation. Another cytoplasmic degradation mechanism is the caspase pathway that is involved in apoptotic cell death. The third method of proteolysis occurs within an organelle called the proteasome. Proteasomes are small organelles composed of protein complexes that are thought to be present in both the cytoplasm and the nucleus. This organelle recognizes misformed and misfolded proteins that have been targeted for degradation, including transcription factors and the cyclins that are important in controlling the cell cycle. It has been suggested that as much as one third of the newly formed polypeptide chains are selected for proteasome degradation because of quality-control mechanisms in the cell.

Mitochondria
The mitochondria are literally the “power plants” of the cell because they transform organic compounds into energy that is easily accessible to the cell. They do not make energy but extract it from organic compounds. Mitochondria contain the enzymes needed for capturing most of the energy in foodstuffs and converting it into cellular energy. This multistep process is often referred to as cellular respiration because it requires oxygen. Cells store most of this energy as high-energy phosphate bonds in compounds such as adenosine triphosphate (ATP), using it to power the various cellular activities. Mitochondria are found close to the site of energy consumption in the cell (e.g., near the myofibrils in muscle cells). The number of mitochondria in a given cell type varies by the type of activity the cell performs and the energy needed to undertake this activity. For example, a dramatic increase in mitochondria occurs in skeletal muscle repeatedly stimulated to contract.
Mitochondria are composed of two membranes: an outer membrane that encloses the periphery of the mitochondrion and an inner membrane that forms shelflike projections, called cristae (Fig. 4.5). The narrow space between the outer and inner membranes is called the intermembrane space, whereas the large space enclosed by the inner membrane is termed the matrix space. The outer mitochondrial membrane contains a large number of transmembrane porins, through which water-soluble molecules may pass. Because this membrane is relatively permeable to small molecules, including proteins, the contents of the intermembrane space resemble that of the cytoplasm. The inner membrane contains the respiratory chain enzymes and transport proteins needed for the synthesis of ATP. In certain regions, the outer and inner membranes contact each other, these contact points serve as pathways for proteins and small molecules to enter and leave the matrix space.
Mitochondria

Mitochondria contain their own DNA and ribosomes and are self-replicating. Mitochondrial DNA (mtDNA) is found in the mitochondrial matrix and is distinct from the chromosomal DNA found in the nucleus. Also known as the “other human genome,” mtDNA is a double-stranded, circular molecule that encodes the rRNA and tRNA required for intramitochondrial synthesis of the proteins needed for the energy-generating functions of the mitochondria. Although mtDNA directs the synthesis of 13 of the proteins required for mitochondrial function, the DNA of the nucleus encodes the structural proteins of the mitochondria and other proteins needed to carry out cellular respiration.
mtDNA is inherited matrilineally (i.e., from the mother), thus providing a basis for familial lineage studies. Mutations have been found in each of the mitochondrial genes, and an understanding of the role of mtDNA in certain diseases is beginning to emerge. Most tissues in the body depend to some extent on oxidative metabolism and can therefore be affected by mtDNA mutations.
Mitochondria also function as key regulators of apoptosis or programmed cell death. The initiation of the mitochondrial pathway for apoptosis results from an increase in mitochondrial permeability and the subsequent release of proapoptotic molecules into the cytoplasm. One of these proapoptotic molecules is cytochrome c, which is bound by cardiolipin (a phospholipid). It is well known for its role in mitochondrial respiration. In the cytosol, cytochrome c binds to a protein called apoptosis activating factor-1, 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 function is to block the apoptotic cascade. Both the formation of reac- tive oxygen species (ROS) (e.g., peroxide) and the activation of the p53 tumor suppressor gene by DNA damage or other means initiate apoptotic signaling through the mitochondria. ROS has been determined to be the etiology of cell injury to multiple diseases. 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 neurodegenerative diseases, in which there is an increased or excessive rate of apoptosis.