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The field of organelle biogenesis has expanded so much in the last few years that it seemed impossible to include a chapter as comprehensive as that found in the last edition of this text without extending the length of the chapter inordinately. Nonetheless, the editors feel that the chapter from the last edition provides an excellent foundation for understanding more recent developments which are now covered throughout the rest of the book where they are relevant to understanding specific diseases of lysosomes, peroxisomes, mitochondria, and membrane receptors. For this reason, we include this chapter from the 7th edition.

  • The eukaryotic cell is surrounded by a plasma membrane and is characterized by the presence of a nucleus and many cytoplasmic organelles, which are functionally specialized and also delimited by membranes. The nucleus is the site of storage and initial decoding of genomic information. Completion of this decoding, however, requires the translation of mRNA in ribosomes present in the cytoplasm and the delivery of each newly synthesized polypeptide to its site of function. This chapter considers the sorting and targeting processes by which newly synthesized proteins are transferred to their sites of function, which may be in the nucleus, in the cytomatrix that occupies the space between organelles, within a membrane, in the luminal cavity of an organelle, or outside the cell. Many genetic diseases lead to defects in specific organellar functions and, in some cases, this results from faulty protein targeting.

  • The plasma membrane and several cytoplasmic organelles, including the ER, Golgi apparatus, secretory granules and vesicles, lysosomes, and endosomes, form an integrated endomembrane system that serves to transfer macromolecules and membrane components from one part of the cell to another, as well as to and from the cell exterior. Many of the proteins of these organelles are synthesized in ribosomes bound to membranes of the ER and are inserted into these membranes, or translocated into the lumen of the ER, during their synthesis. These proteins can then either remain within the ER or be transported along the endomembrane system by a process that involves their incorporation into vesicles. These vesicles are formed by budding from the membrane of a donor compartment and deliver their content by fusing with a membrane of the acceptor compartment. We discuss in detail the mechanisms that: (1) select specific mRNA for translation in ribosomes associated with the ER, (2) determine the transmembrane disposition of integral membrane proteins, (3) mediate the retention of proteins in a specific organelle, or their transport within the endomembrane system, and (4) lead to the production of vesicles in a donor membrane and determine their fusion with a specific acceptor membrane.

  • Mitochondria and peroxisomes are organelles that do not communicate with the endomembrane system through vesicular flow and acquire their protein contents by direct uptake of newly synthesized, but not yet fully folded, polypeptides from the cytoplasm. The uptake into mitochondria involves molecular chaperones, as well as receptors on ...

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