The Biogenesis of Cellular Organelles.
Mullins C
BOOK (2005)
Category: endocytosis, endoplasmic reticulum, lipid rafts, mitochondria, mitochondria-biogenesis, nucleus, Organelle biogenesis, peroxisome, vacuole ¤ Added: Apr 26, 2009 ¤ Rating: ◊◊
The evolution of modern cell biology tools, such as confocal imaging techniques and advanced electron microscopy methodologies, has allowed for ever improving structural and functional characterizations of the cell. Such methods complement classical genetics and biochemistry in the ongoing effort to define cellular science. This is especially apparent in the area of organelle biology. Studies dating back over 100 years to the present have revealed the elaborate collection of distinctive membrane-bound cytoplasmic subcompartments, termed organelles, within the eukaryotic cell and defined their roles in mediating numerous specialized functions in cellular physiology. Organelles play an essential role in the cell in large part through ensuring a tight regulatory and functional separation of distinct chemical reactions, such as cellular respiration, and molecular processes, such as protein degradation and DNA replication. Many organelles are common to virtually all cell types (e.g., the nucleus) while others reside only in certain differentiated cells (e.g., the lysosome-related lytic granules and melanosomes found in cytotoxic T lymphocytes and melanocytes, respectively). The unique characteristics of such heterogeneous cellular organelles are dictated by their particular biochemical composition and complement of biomolecules. The Biogenesis of Cellular Organelles seeks to describe the cellular and molecular mechanisms mediating the biogenesis, maintenance, and function of key eukaryotic organelles. This work consists of an initial discussion of the evolution of organelle biogenesis theory from early studies through recent findings, overviews of the prominent cellular machineries involved in the biogenesis and maintenance of cellular organelles, and reviews of the function and biogenesis of a number of key organelles common to nearly all eukaryotic cells, including the endoplasmic reticulum, the Golgi apparatus, the lysosome, the nucleus, the mitochondria, and the peroxisome. All chapters strive to highlight recent findings and topical issues relating to organelle biology. The primary interests of this work are the biogenesis and functional events operating in mammalian cells and in some cases the analogous events in key lower eukaryotes, such as yeast and Drosophila. The reader should note that a wealth of organelles besides those covered here have also been described, such as the all important chloroplast present in plants and other photosynthetic organisms. The general themes of each chapter are as follows: Chapter one offers a historical perspective of organelle biogenesis. This chapter recounts early discoveries that formed the foundation for the modern study of organelle biology, including the role of protein sorting in organelle maintenance and methods of organelle inheritance during cell division. In this chapter the progression from early findings to more recent discoveries in developing our current views of organelle function and biogenesis are highlighted. Chapter two presents an in depth discussion of protein coats, which in concert with additional components of the cellular machinery operate to selectively sort proteins within intracellular and endocytic trafficking pathways. In this function protein coats serve as key mediators of organelle biogenesis and maintenance. The protein coat constituents described include the adaptor protein (AP) complexes and clathrin, which operate in the late-secretory and endocytic pathways, and the COP complexes, which operate in the early secretory pathway. The recently defined adaptor-related coat proteins, the GGAs and Stoned B family members, are also reviewed. Chapter three describes the cooperative role played by lipids and proteins in maintaining organelle identity and function in the face of continuous biomolecular flux between compartments and to and from the plasma membrane. The key players mediating compartment identity described include the ARF and Rab GTPases, the inositol phospholipids, and members of the SNARE protein family. Chapter four provides an extensive description of the organization, function, and maintenance of the endoplasmic reticulum. The remarkably dynamic nature and morphological variability of the endoplasmic reticulum are detailed along with its numerous cellular roles, including serving as the primary site for membrane protein synthesis and entry into the secretory pathway. The contribution of proliferation and differentiation of existing membranes to the generation of endoplasmic reticulum networks are also reviewed. Chapter five reviews classical and recent findings relating to the Golgi apparatus, which functions as a site for post-translational modifications of glycoproteins and glycolipids and for the selective sorting of secretory proteins to the plasma membranes or target sites within the cell. The complex morphology of the Golgi, which allows compartmentalization of distinct Golgi functions, and the dynamics of its disassembly and reassembly during the cell cycle are highlighted. Chapter six discusses the function and biogenesis of the lysosome. The role of the lysosome, and the analogous yeast vacuole, as the primary degradative compartment in the cell and current models for the biogenesis of lysosomes and related compartments are discussed. The participation of the protein sorting machinery in lysosomal maintenance and function are described. Also, the importance of the lysosome to cellular function is illustrated through discussions of a number of mutant phenotypes resulting from perturbation of lysosomal protein sorting. Chapter seven offers a review of nuclear biogenesis, or nucleogenesis. This chapter focuses on the dynamic disassembly and reassembly of the nuclear envelope during mitotic division and the cellular machinery mediating these processes. The biogenesis of nucleoli, the nuclear structures that serve as sites for ribosome biosynthesis, is also detailed. Chapter eight reviews the function, intricate structure, and biogenesis of the mitochondria, which serves as the site of cellular respiration. The unique nature of this organelle, which has prokaryotic origins and still retains it own small genome, is described, as is its essential nature in the physiology of the cell. The mode of mitochondrial biogenesis through growth and division of pre-existing mitochondria is detailed. The pathways for mitochondrial protein import and export and ion trafficking are also reviewed. Chapter nine presents an overview of peroxisome biogenesis and function. Potential modes of formation of the peroxisome, which represent an organelle rich in metabolic enzymes and activities, are discussed along with cellular factors that contribute to its biogenesis and function. This work also details the numerous peroxisomal disorders in humans, which highlights the need to address the many unanswered questions regarding the biology of this important organelle. While the discoveries described in The Biogenesis of Cellular Organelles and elsewhere illustrate our growing understanding of the fundamental processes mediating organelle biogenesis and function, they also remind us of how much remains to be discovered. The pursuit of knowledge regarding organelle biology is essential to understanding the basic science of the cell as well as human physiology. This is clearly evident from the growing observations that associate defects in organelle function to human disease. With the continued dedication of basic and clinical scientists to addressing these important questions ensured, the future of cellular biology is sure to be one of remarkable discovery.