of the system (and the excitement about its genetic engineering potential) comes from its impressive flexibility and specificity, which is substantially better than other previous editing systems. Applications include inserting specific mutations into the genomes of cells to model cancers and other diseases, and rapidly generating transgenic animals from edited embryonic stem cells. On the flip side, it now is feasible to selectively “correct” mutations that cause hereditable disease, or—perhaps more worrisome—to just eliminate less “desirable” traits. Predictably, the technology has inspired a vigorous debate regarding its application.
The viability and normal activity of cells depend on a variety of fundamental housekeeping functions that all differentiated cells must perform.
Many normal housekeeping functions are compartmentalized within membrane-bound intracellular organelles (
Fig. 1.6 ). By isolating certain cellular functions within distinct compartments, potentially injurious degradative enzymes or reactive metabolites can be concentrated or stored at high concentrations in specific organelles without risking damage to other cellular constituents. Moreover, compartmentalization allows for the creation of unique intracellular environments (e.g., low pH or high calcium) that are optimal for certain enzymes or metabolic  pathways.
New proteins destined for the plasma membrane or secretion are synthesized in the rough endoplasmic reticulum (RER) and physically assembled in the Golgi apparatus; proteins intended for the cytosol are synthesized on free ribosomes. Smooth endoplasmic reticulum (SER) may be abundant in certain cell types such as gonads and liver where it serves as the site of steroid hormone and lipoprotein synthesis, as well as the modification of hydrophobic compounds such as drugs into water-soluble molecules for export.
Cells catabolize the wide variety of molecules that they endocytose, as well as their own repertoire of proteins and organelles—all of which are constantly being degraded and renewed. Breakdown of these constituents takes place at three different sites, ultimately serving different  functions.
Proteasomes are “disposal” complexes that degrade denatured or otherwise “tagged” cytosolic proteins and release short peptides. In some cases the peptides so generated are presented in the context of class I major histocompatibility molecules to help drive the adaptive immune response (Chapter 5). In other cases, proteasomal degradation of regulatory proteins or transcription factors can trigger or shut down cellular signaling pathways.
Lysosomes are intracellular organelles that contain enzymes that digest a wide range of macromolecules, including proteins, polysaccharides, lipids, and nucleic acids. They are the organelle in which phagocytosed microbes and damaged or unwanted cellular organelles are degraded and eliminated.
Peroxisomes are specialized cell organelles that contain catalase, peroxidase and other oxidative enzymes. They
Relative volumes of intracellular organelles (hepatocyte)
Compartment % total volume number/cell role in the cell
Cytosol 54% 1 metabolism, transport, protein translation Mitochondria 22% 1700 energy generation, apoptosis Rough ER 9% 1* synthesis of membrane and secreted proteins Smooth ER, Golgi 6% 1* protein modification, sorting, catabolism Nucleus 6% 1 cell regulation, proliferation, DNA transcription Endosomes 1% 200 intracellular transport and export, ingestion of extracellular substances Lysosomes 1% 300 cellular catabolism Peroxisomes 1% 400 very long-chain fatty acid metabolism