An animal cell contains about 10 billion (10^10) protein molecules of perhaps 10,000 kinds, and the synthesis of almost all of them begins in the cytosol, the space of the cytoplasm outside the membrane-enclosed organelles. Each newly synthesized protein is then delivered specifically to the organelle that requires it. By tracing the protein traffic from one compartment to another, one can begin to make sense of the otherwise bewildering maze of intracellular membranes.
The Compartmentalization of Cells
All Eukaryotic Cells Have the Same Basic Set of Membraneenclosed Organelles
Many vital biochemical processes take place in membranes or on their surfaces. Membrane-bound enzymes, for example, catalyze lipid metabolism; and oxidative phosphorylation and photosynthesis both require a membrane to couple the transport of H+ to the synthesis of ATP. In addition to providing increased membrane area to host biochemical reactions, intracellular membrane systems form enclosed compartments that are separate from the cytosol, thus creating functionally specialized aqueous spaces within the cell. In these spaces, subsets of molecules (proteins, reactants, ions) are concentrated to optimize the biochemical reactions in which they participate. Because the lipid bilayer of cell membranes is impermeable to most hydrophilic molecules, the membrane of an organelle must contain membrane transport proteins to import and export specific metabolites. Each organelle membrane must also have a mechanism for importing, and incorporating into the organelle, the specific proteins that make the organelle unique.
Figure 12–1 illustrates the major intracellular compartments common to eukaryotic cells. The nucleus contains the genome (aside from mitochondrial and chloroplast DNA), and it is the principal site of DNA and RNA synthesis. The surrounding cytoplasm consists of the cytosol and the cytoplasmic organelles suspended in it. The cytosol constitutes a little more than half the total volume of the cell, and it is the main site of protein synthesis and degradation. It also performs most of the cell’s intermediary metabolism—that is, the many reactions that degrade some small molecules and synthesize others to provide the building blocks for macromolecules (discussed in Chapter 2). About half the total area of membrane in a eukaryotic cell encloses the labyrinthine spaces of the endoplasmic reticulum (ER). The rough ER has many ribosomes bound to its cytosolic surface. Ribosomes are organelles that are not membrane- enclosed; they synthesize both soluble and integral membrane proteins, most of which are destined either for secretion to the cell exterior or for other organelles. We shall see that, whereas proteins are transported into other membrane- enclosed organelles only after their synthesis is complete, they are transported into the ER as they are synthesized. This explains why the ER membrane is unique in having ribosomes tethered to it. The ER also produces most of the lipid for the rest of the cell and functions as a store for Ca2+ ions. Regions of the ER that lack bound ribosomes are called smooth ER. The ER sends many of its proteins and lipids to the Golgi apparatus, which often consists of organized stacks of disclike compartments called Golgi cisternae. The Golgi apparatus receives lipids and proteins from the ER and dispatches them to various destinations, usually covalently modifying them en route. Mitochondria and chloroplasts generate most of the ATP that cells use to drive reactions requiring an input of free energy; chloroplasts are a specialized version of plastids (present in plants, algae, and some protozoa), which can also have other functions, such as the storage of food or pigment molecules. Lysosomes contain digestive enzymes that degrade defunct intracellular organelles, as well as macromolecules and particles taken in from outside the cell by endocytosis. On the way to lysosomes, endocytosed material must first pass through a series of organelles called endosomes. Finally, peroxisomes are small vesicular compartments that contain enzymes used in various oxidative reactions. In general, each membrane-enclosed organelle performs the same set of basic functions in all cell types. But to serve the specialized functions of cells, these organelles vary in abundance and can have additional properties that differ from cell type to cell type.
On average, the membrane-enclosed compartments together occupy nearly half the volume of a cell (Table 12–1), and a large amount of intracellular membrane is required to make them. In liver and pancreatic cells, for example, the endoplasmic reticulum has a total membrane surface area that is, respectively, 25 times and 12 times that of the plasma membrane (Table 12–2). The membrane- enclosed organelles are packed tightly in the cytoplasm, and, in terms of area and mass, the plasma membrane is only a minor membrane in most eukaryotic cells (Figure 12–2). The abundance and shape of membrane-enclosed organelles are regulated to meet the needs of the cell. This is particularly apparent in cells that are highly specialized and therefore disproportionately rely on specific organelles. Plasma cells, for example, which secrete their own weight every day in antibody molecules into the bloodstream, contain vastly amplified amounts of rough ER, which is found in large, flat sheets. Cells that specialize in lipid synthesis also expand their ER, but in this case the organelle forms a network of convoluted tubules. Moreover, membrane-enclosed organelles are often found in characteristic positions in the cytoplasm. In most cells, for example, the Golgi apparatus is located close to the nucleus, whereas the network of ER tubules extends from the nucleus throughout the entire cytosol. These characteristic distributions depend on interactions of the organelles with the cytoskeleton. The localization of both the ER and the Golgi apparatus, for instance, depends on an intact microtubule array; if the microtubules are experimentally depolymerized with a drug, the Golgi apparatus fragments and disperses throughout the cell, and the ER network collapses toward the cell center (discussed in Chapter 16). The size, shape, composition, and location are all important and regulated features of these organelles that ultimately contribute to the organelle’s function.
To understand the relationships between the compartments of the cell, it is helpful to consider how they might have evolved. The precursors of the first eukaryotic cells are thought to have been relatively simple cells that—like most bacterial and archaeal cells—have a plasma membrane but no internal membranes. The plasma membrane in such cells provides all membrane-dependent functions, including the pumping of ions, ATP synthesis, protein secretion, and lipid synthesis. Typical present-day eukaryotic cells are 10–30 times larger in linear dimension and 1000–10,000 times greater in volume than a typical bacterium such as E. coli. The profusion of internal membranes can be regarded, in part, as an adaptation to this increase in size: the eukaryotic cell has a much smaller ratio of surface area to volume, and its plasma membrane therefore presumably has too small an area to
sustain the many vital functions that membranes perform. The extensive internal membrane systems of a eukaryotic cell alleviate this problem.
The evolution of internal membranes evidently went hand-in-hand with the specialization of membrane function.
Why is that evident ? Thats not evident at all.
A hypothetical scheme for how the first eukaryotic cells, with a nucleus and ER, might have evolved by the invagination and pinching off of the plasma membrane of an ancestral cell is illustrated in Figure 12–3.This process would create membrane-enclosed organelles with an interior or lumen that is topologically equivalent to the exterior of the cell. We shall see that this topological relationship holds for all of the organelles involved in the secretory and endocytic pathways, including the ER, Golgi apparatus, endosomes, lysosomes, and peroxisomes. We can therefore think of all of these organelles as members of the same topologically equivalent compartment. As we discuss in detail in the next chapter, their interiors communicate extensively with one another and with the outside of the cell via transport vesicles, which bud off from one organelle and fuse with another (Figure 12–4).
Mitochondria and plastids differ from the other membrane-enclosed organelles because they contain their own genomes. The nature of these genomes, and the close resemblance of the proteins in these organelles to those in some present-day bacteria, strongly suggest that mitochondria and plastids evolved from bacteria that were engulfed by other cells with which they initially lived in symbiosis (see Figures 1–29 and 1–31): the inner membrane of mitochondria and plastids presumably corresponds to the original plasma membrane of the bacterium, while the lumen of these organelles evolved from the bacterial cytosol. Like the bacteria from which they were derived, both mitochondria and plastids are enclosed by a double membrane and they remain isolated from the extensive vesicular traffic that connects the interiors of most of the other membrane-enclosed organelles to each other and to the outside of the cell.