MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. CHAPTER 4: A JOURNEY INTO THE EUKARYOTIC CELL - Part 2 – The two hallmark features of all eukaryotic cells are the presence of a nucleus and of so-called organelles within the cells Organelles are phospholipid membrane-made (= membranous) compartments of different shape and function within eukaryotic cells which we will look up in more detail in this section. These membranes and compartment participate in many aspects of cellular metabolism as many enzymes are built into membranes. Also, the barriers created by these intracellular membranes provide different local environments that facilitate specific metabolic functions. Schematic presentation of an eukaryotic cell & Major organelles 1 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. The organelles and structures of eukaryotic cells The key characteristics of eukaryotic cells is that they have a true nucleus - the nucleus is separated from the cytoplasm via a double nuclear membrane (or nuclear envelope, - the nucleus averages about 5 microns in diameter - where the double membranes are fused, a pore, the nuclear pore, allows large macromolecules, gene regulating proteins (transcription factors) and particles to pass through in a highly regulated fashion - the pores enable exchange of e.g. proteins and communication with the cytosol, e.g. the messenger RNA leaves the nucleus via pores to reach the ribosomes - the nuclear side of the envelope is lined by the nuclear lamina, a network of intermediate filaments that maintain the shape of the nucleus - a key protein of the nuclear lamina is lamin - a mutated version of lamin has been found in humans suffering from the “accelerated aging disease” Progeria 2 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. The nucleus is the genetic control center and harbors the chromosomal DNA - DNA is attached to special proteins, e.g. Histones; - the formed, long DNA/protein fibers are called chromatin; - each fiber builds a so-called chromosome - within a normal cell chromatin appears as diffuse mass. - however when the cell prepares to divide, the chromatin fibers coil up to be seen as separate structures, called chromosomes. - each eukaryotic species has a characteristic number of chromosomes. - a typical human cell has 46 chromosomes, but sex cells (eggs and sperm) have only 23 chromosomes The nucleus directs protein synthesis by synthesizing messenger RNA (mRNA) from the cell’s genes via a cellular process called DNA Transcription. The mRNA leaves the nucleus via the nuclear pores and travels via the cytoplasm to the rough endoplasmic reticulum (rER). There it combines with ribosomes to translate its genetic message into the primary structure of a specific polypeptide. The nucleolus (found within the nucleus) consists of DNA, RNA and specific proteins, such as nucleolin - in the nucleolus, ribosomal RNA (rRNA) is synthesized and assembled with proteins from the cytoplasm to form ribosomal subunits - the subunits pass from the nuclear pores to the cytoplasm where they combine to form ribosomes. TThhee nnuucclleeuuss ((w wiitthh nnuucclleeoolluuss)) 3-D Model electron microscopic image All eukaryotic cells are surrounded by a plasma membrane. The plasma membrane is the outer cell barrier. It is made of mainly phospholipids, which form a so-called lipid bilayer. It completely encloses the cytoplasm and all the other cellular structures and components. - the plasma membrane also contains many proteins, which are inserted (or intercalated) into its lipid matrix 3 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. - many of these proteins serve as docking sites (= receptors) for hormones or disease-causing viruses (e.g. HIV, flu) TThhee cceellll m meem mbbrraannee 3D-model Electron microscopic image Eukaryotic cells have multiple, membranous compartments or so-called organelles. Many of the internal membranes in a eukaryotic cell are part of the endomembrane system. The endomembrane system includes the nuclear envelope, endoplasmic reticulum, Golgi apparatus, lysosomes, vacuoles, and the plasma membrane. These membranes are either in direct contact or connected via transfer of vesicles, sacs of membrane. - in spite of these links, these membranes have diverse functions and structures The 7 major types of these membranous organelles known in eukaryotes are: 1. Rough endoplasmic reticulum (rER) From Greek, which means ‘network within the cell’ The rER is connected with the nuclear envelope but not with other organelles the only connection to other organelles, such as the Golgi apparatus, is via socalled transport vesicles 4 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. The rER includes membranous tubules and internal, fluid-filled spaces, the cisternae. The ER membrane is continuous with the nuclear envelope and the cisternal space of the ER is continuous with the space between the two membranes of the nuclear envelope. This organelle is called rough ER, because in the electron microscope the membrane surface looks ‘rough’ due to studded ribosomes on its surface! The primary function of the rER is the production of new biological membrane due to synthesis of new phospholipids from precursors in the cytosol. - as the ER membrane expands, parts can be transferred as transport vesicles to other components of the endomembrane system. The secondary function is the synthesis of new protein at the ribosomes (= protein translation) The rER is also the place where newly synthesized polypeptide strands are folded into functional proteins the ‘folding helper’ proteins located within the cisternae are called called chaperones The rER is also the site where sugar residues are attached to proteins to form so-called glycoproteins In the rER newly produced and shaped proteins are made ready for its export or its final destination within the cell At the outer stretches of the rER, proteins are packaged into little, round phospholipidmade sacs, so-called transport vesicles, which are pinched-off and directed towards the so-called Golgi apparatus. 5 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. 2. S Sm mooootthh eennddooppllaassm maattiicc rreettiiccuulluum m (sER or ER) 3D-Model The sER is not a direct continuation of the rER but rather an independent organelle with more specialized functions The smooth ER is called “smooth” because under an electron microscope it does not show any ribosomes associated with its membrane. But the sER rich in enzymes and plays a role in a variety of metabolic processes. Enzymes of the smooth ER synthesize lipids, including oils, phospholipids, and steroids. - the latter includes the sex hormones of vertebrates and adrenal steroids. The smooth ER also catalyzes a key step in the mobilization of glucose from stored glycogen in the liver. An enzyme removes the phosphate group from glucose phosphate, a product of glycogen hydrolysis, permitting glucose to exit the cell. Other enzymes in the smooth ER of the liver help detoxify drugs and poisons. These include alcohol and barbiturates. - frequent exposure leads to proliferation of smooth ER, increasing tolerance to the target and other drugs. The sER is also the major cellular storage place of calcium ions (Ca2+) - calcium plays an important role for muscle contraction (especially in muscle cells) an in the transmission of cellular signals (signal transduction); - when nerve impulse stimulates a muscle cell, calcium rushes from the ER into the cytosol, triggering contraction. - calcium transporter proteins then pump the calcium back, readying the cell for the next stimulation. 6 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. TThhee G Goollggii aappppaarraattuuss ((oorr nneettw woorrkk)) & Transport vesicles 3. ← Transport Vesicle The Golgi network consists of multiple stacks of flattened phospholipid sacs - cisternae looking like a sac of pita bread. The membrane of each cisterna separates its internal space from the cytosol. One side of the Golgi, the cis side, it receives material, e.g. proteins, by fusing with transport vesicles, while the other side, the trans side, buds off vesicles that travel to other sites. During their transit from the cis to trans pole, products from the ER are modified to reach their final state. - this includes modifications of the oligosaccharide portion of glycoproteins. - the Golgi can also manufacture its own macromolecules, including pectin and other noncellulose polysaccharides. - during processing material is moved from cisterna to cisterna, each with its own set of enzymes Many Golgi structures are visible in heavily secreting cells - e.g. mast cells: they release huge amounts of histamine in allergic reactions The Golgi network is the cellular protein sorting center. Many transport vesicles from the ER travel to the Golgi apparatus for modification of their contents. - the Golgi is a center of manufacturing, warehousing, sorting, and shipping. The Golgi apparatus is especially extensive in cells specialized for secretion. 7 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. M Miittoocchhoonnddrriioonn (Plural: Mitochondria) 4. 3-D Model Electron microscopic image Mitochondria are the sites of cellular respiration, generating ATP from the catabolism of sugars, fats, and other fuels in the presence of oxygen. Mitochondria convert energy received from chemical degradation reactions (= catabolic metabolism) into the synthesis of novel chemical compounds It is the place of cellular respiration, in which the energy of sugars, e.g. glucose or fructose is converted and stored into the chemical energy of the cell’s ‘energy currency’ ATP. Therefore biologists often speak of the mitochondrion as the cellular power plant which makes the cellular fuel ATP 8 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. A typical mitochondrion is 1-10 microns long and is enclosed by two biological phospholipid membranes (= inner- and outer membrane) The inner membrane is highly folded into so-called cristae. Many enzymes involved in cellular respiration and ATP synthesis are embedded into this important membrane which is the place of the electron transport chain (= ETC) The mitochondrion has two compartments 1. intermembrane space = fluid-filled compartment 2. mitochondrial matrix = compartment enclosed by the inner membrane = place where all the major chemical reactions of cellular respiration and parts of the Krebs cycle occur Mitochondria contain their own mitochondrial DNA (= mtDNA) - the DNA is circular and resembles that of a bacterium in its basic structure - this DNA is to 99.9% inherited from the mother - analysis of mtDNA became an important tool in forensic investigations 9 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. Mitochondria have (most) of the components necessary for making their own proteins (= protein synthesis) - they have their own ribosomes and tRNA molecules - they contain 22 tRNAs, rRNAs (16S,12S & 5S) Mitochondria play also an important role in the initial cellular processes which lead to programmed cell death (= Apoptosis) Mitochondria replicate autonomously from the cell by undergoing binary fission, much like bacterial cells. This process involves a furrowing of the inner and then the outer membrane. Almost all eukaryotic cells have mitochondria. There may be one very large mitochondrion or hundreds to thousands in individual mitochondria. The number of mitochondria is correlated with aerobic metabolic activity. Mitochondria are quite dynamic: moving, changing shape, and dividing. Some, rare diseases, mostly manifesting in aging patients, are connected to mutations of mtDNA e.g. Leber's hereditary optic neuropathy (degeneration of the optic nerve, accompanied by increasing blindness): caused by mutation to the gene encoding the ETC enzyme NADH-CoQ reductase e.g. mitochondria of a patient suffering from Luft disease could make only a fraction of the energy they should normally produce 5. C Chhlloorrooppllaassttss (only in ggrreeeenn aallggeeaa,, ddiiaattoom mss aanndd ppllaanntt cceellllss!!) 3-D Model Electron microscopic image 10 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. It is the organelle in green algea, diatoms and plants where photosynthesis takes place The chloroplast plays the crucial role in the plants unique ability to convert solar (= light) energy into the chemical energy of sugar molecules The chloroplast consists of 3 major compartments 1. Inner – and outer membrane made of phospholipids 2. Stroma place enclosed by the inner membrane, filled with a thick fluid and a dense network of tubules and hollow, disc-like structures, called thylacoids contains the soluble enzymes responsible for the dark reactions of photosynthesis contains the chloroplast DNA and ribosomes 3. Thylacoids the thylacoid membranes harbor the ‘molecular solar panels’, which consist of an array of proteins containing chlorophyll molecules thylacoids are organized in stacks, each called a granum Although the DNA of the plant cell nucleus codes the majority of chloroplast proteins, chloroplasts contain (similar to mitochondria) their own (extrachromosomal) DNA and ribosomes the 121,024 nucleotide base pair long chloroplast DNA of liverwort contains 128 possible genes, including genes for four kinds of ribosomal RNA, 32 species of transfer RNA genes, and 55 possible genes for proteins 17-20 million-year-old DNA was isolated from fossilized chloroplasts of leaves of a magnolia and a bald cypress found in Miocene sediments at Clarkia, Idaho Chloroplasts are susceptible to many toxins and are the target of many fungal pathogens most of the common herbicides (such as Paraquat) target and destroy the chloroplast’s membranes and electron transport chains, e.g. by releasing free radicals and other toxic by-products e.g. the fungus Fusarium solani produces naphthazarin toxins, which destroy chloroplast membranes causing plant wilting and bleaching of chlorophyll Conditions commonly referred to as “oxidative stress”, usually caused by strong UV light (= UV-C), ozone, hydrogen peroxide and other chemical oxidants 11 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. ( see Paraquat) , are suspected to disrupt the coordinated flow of electrons in the thylacoid membranes and in the photosystems leading to plant damage and eventual death 66.. LLyyssoossoom meess 3-D model Electron microscopic image Lysosomes are very small, highly specialized cellular organelles The lysosome is a membrane-bounded sac containing a variety of hydrolytic enzymes, including lipases, DNAases, proteases, that digest macromolecules. Lysosomal enzymes can hydrolyze proteins, fats, polysaccharides, and nucleic acids. The interior of lysosomes is acidic since the hydrolytic lysosome enzymes work best at pH 5. To keep the interior acidic, proteins in the lysosomal membrane pump hydrogen ions from the cytosol to the lumen of the lysosomes. While rupturing of one or a few lysosomes has little impact on a cell, massive leakage of the enzymes from lysosomes can destroy an cell by autodigestion. These lysosomal enzymes also play a major role in the destruction of invaded bacteria or microorganisms - e.g. in white blood cells/phagocytes Lysosomes play an important role in the digestion of food particles taken up via endocytosis and in the control of the mitochondrial numbers within a cell by preparing for a digestive process called autophagy. - as the polymers of the food are digested, their monomers pass out to the cytosol to become nutrients of the cell. - when lysosomes fuse with another (not further used) organelle or part of the cytosol in order to break its components down into its monomers, this recycling process is referred to as autophagy. 12 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. Lysosomes are important for normal cell function and human health e.g. several lysosomal storage diseases are known: 1. Pompe’s disease the liver lysosomes lack glycogen degrading enzymes 2. Tay-Sachs disease the lysosomes of nerve cells lack lipid-degrading enzymes 13 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology Lecture (BIOL 107): Instructor: Elmar Schmid, Ph.D. 14 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. 77.. P Peerrooxxiissoom meess Electron microscopic image The peroxisome is another very small but highly specialized organelle which has multiple functions: 1. it is responsible for the degradation (= -oxidation) of long and branchedchain fatty acids peroxisomal malfunction can result in a set of disorders known as the -oxidation disorders or also referred to as the pseudo-Zellweger syndrome when a peroxisome is not able to breakdown dietary Phytanic acids, this impairment results in a disorder called Refsum disease 2. it plays a fundamental role in the synthesis of important biomolecules, such as cholesterol, bile acids and special memebrane lipids (= plasmalogens) 3. it is involved in the degradation of aggressive biocompounds, such as hydrogen peroxide Genetic defects in peroxisome assembly cause Graves disease in humans 15 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. E Euukkaarryyoottiicc cceellllss hhaavvee ootthheerr uunniiqquuee,, nnoonn--oorrggaanneellllee ssttrruuccttuurreess 1. Flagella and cilia Several structures can be found in eukaryotic cells which are differently sized plasma membrane protrusions. Important cell protrusions are: flagella (singular: flagellum), cilia (singular: cilium) and microvilli (singular: microvillus). - flagella are only found in highly specialized animal or plant cells, called sperm, and are also visible on single-celled life forms called dinoflagellates; they allow fast motion and movement of these cells; - cilia are found on the apical surface of highly specialized cells, called epithelial cells, which form the inner lining of ducts within animals or human bodies, such as the Fallopian tubes and the trachea; there they help to propel mucous, the egg cell, or debris, across the surface; - microvilli are found on the apical surface of the epithelial cells which are lining the intestinal tube of animals and humans; they help to increase the surface in that region for improved uptake (resorption) of food molecules; Cilia and flagella are membrane projections from the cell, which internally are stabilized by tube-like protein structures called micro-tubules. The microtubules are build through polymerization of a protein monomer called tubulin The microvilli are rather small and short membrane projections which internally are stabilized by protein fibers called microfilaments. The microfilaments are build through polymerization of a protein monomer called actin. The primary purpose of flagella and cilia, which have the same internal microtubule structure, is movement and cellular dynamic; cilia move fluid, mucous, or other cells over their surface FFllaaggeellllaa sperm (left panel) or dinoflagellate (right panel) 16 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. C Crroossss sseeccttiioonn ooff aa cciilliiuum m M Miiccrroottuubbuullee m mooddeell 17 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. 2. Cell wall (only in ppllaanntt cceellllss!!) the cell wall is made of the polysaccharide cellulose and surrounds the plasma membrane it gives the plant cells protection, support and rigidity 3. Vacuoles (only in pprroottiissttss and ppllaanntt cceellllss!) membranous sacs with a variety of functions: 1. food vacuole: degradation of internalized nutrients with the help of fused lysosomes 2. central vacuole helps plants to grow by water absorption, storage of nutrients and metabolic waste products storage of pigments, protective compounds and plant poisons (= repellents) 3. contractile vacuole e.g. in the protist Paramecium; helps to expel excess water from the cell interior eukaryotic cells also have several non-membranous structures or macromolecules: Microtubule-Organizing Complex (= MTOC) & Centrioles the MTOC, which contains two microtubule-made centrioles, are the cellular start site of the formation of the so-called microtubular spindle apparatus which is necessary during mitosis or meiosis (see Chapter 8) The Cytoskeleton The cytoskeleton is an extensive network of thin protein fibers which extends throughout the cytoplasm. The cytoskeleton has several important functions for a cell: 1. It organizes the structures and activities of the cell 2. It provides mechanical support and maintains shape of the cell. - the fibers act like a geodesic dome to stabilize a balance between opposing forces. 3. It provides anchorage for many organelles and cytosolic enzymes. 4. It confers dynamics and motility to a cell - it can dismantle in one part of a cell while reassembling in another part e.g. to change the cell’s shape 18 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. 5. It is important for cell transport of materials. - cytoskeletal fibers, most importantly microtubules, serve as cellular ‘mono-rails’ along which ATP-powered motor proteins carry transport vesicles or organelles to various destinations. 6. It is important for circulation of materials within a cell via streaming. Recently, evidence is accumulating that the cytoskeleton may transmit mechanical signals that rearrange the nucleoli and other structures. The cytoskeleton also plays a major role in cell motility which involves ATPdependent motor proteins, most importantly dynein, and involves different cell structures 1. Flagella - these are 10-200 micrometer long cell protrusions filled with 9+2 arranged microtubules and ATP-driven motor proteins - they allow fast movement of cells, e.g. sperm 19 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. 2. Cilia - short (2-20 micrometer) cell protrusions which help to move unicellular and small multicellular organisms by propelling water past the organism. - important function in tissues of multicellular life forms where they help to move fluid and other materials over a surface. - e.g. cilia sweep mucus carrying trapped debris from the lungs. - Cilia move more like oars with alternating power and recovery strokes. They generate force perpendicular to the cilia’s axis. 20 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. 3. Pseudopodia The cytoskeleton interacts with ATP-hydrolyzing motor proteins, most prominently dynein. In cilia and flagella motor proteins pull components of the cytoskeleton past each other. The cytoskeleton which is a supportive cellular meshwork of fine protein fibers consists of 3 major classes of protein monomers: 1. Microfilaments - these are solid helical fibers which are build through polymerization of the globular protein monomer actin - an actin microfilament consists of a twisted double chain of actin subunits - microfilaments are mostly located under the plasma membrane where they form a cortical network of fibers - they help to maintain the cell shape and are involved in the amoeboid cell movement and migration through formation of pseudopodia (“fake legs”) - they build the core components of short and thin cell protrusions called microvilli 21 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. which are found on the lumen side of cells of the gastrointestinal tract in animals and humans - microfilaments are destroyable by certain drugs, e.g. cytochalasin B 2. Intermediate filaments (IFs or 10nm fibers) - they help to reinforce the cell for bearing tensions - they play a key role in the proper placement of organelles and the nucleus within the cell - they are connected with tight junctions, desmosomes and other important cell contact mediating structures 3. Microtubules - the thickest of all cytoskeletal fibers - they are hollow rods with about 25 micrometer in diameter. - they are constructed via polymerisation of the globular protein called tubulin - they can grow or shrink as more tubulin molecules are added or removed. - they guide the movemnent of chromosomes during cell division. - they serve as protein tracks that guide motor proteins carrying organelles or transport vesicles to their destination. 22 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. - e.g. key role in axonal transport of neurotransmitter-containing vesicles in nerve cells - they are the core components of cilia and flagella - they are the molecular basis for ciliar and flagellar movement - they can be destroyed by certain synthetic or plant-derived drugs, e.g. colchicine, vinblastine and taxol; some of the known microtubuli-destroying drugs, such as Taxol, play an important role in modern cancer therapy TThhee 33 m maajjoorr ccoom mppoonneennttss ooff tthhee cceelllluullaarr ccyyttoosskkeelleettoonn 23 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. R Riibboossoom meess Ribosomes are huge protein/RNA complexes which are the site of active protein synthesis (= translation) in prokaryotic and eukaryotic cells. It is made up from two (one small and one large) protein units and associated RNA molecules, most importantly rRNA and tRNA molecules. While in prokaryotic cells (bacteria), ribosomes are freely floating within the cytosol, in eukaryotic cells, ribosomes are attached to the outer membrane surfaces of the rough endoplasmatic reticulum S Sttrruuccttuurraall m mooddeell ooff aa bbaacctteerriiaall rriibboossoom mee P Prrootteeaassoom mee The proteasome is huge, hollow, barrel-shaped protein complex which is found located within the cyctosol It serves as a cellular “protein shredder” and is the site of controlled protein degradation within the cell This organelle is important for proteolytic degradation of endogenous proteins (proteins synthesized within cell), such as transcription factors, cell cycle cyclins, virus coded proteins, improperly folded (faulty) proteins due to translation errors (made by mutated genes) and proteins damaged by cytosol molecules Proteosome dysfunction seems to play a role in human diseases, such as cystic fibrosis. This fatal human hereditary disease is due to the accelerated degradation of a chloride transporter protein by the proteasome 24 MESA COLLEGE, SAN DIEGO SCHOOL OF MATHEMATICS & NATURAL SCIENCE General Biology (BIOL 107): Instructor: Elmar Schmid, Ph.D. The Proteasome W Whhyy ddoo eeuukkaarryyoottiicc cceellllss hhaavvee oorrggaanneelllleess?? 1. Many of the cells crucial chemical reactions = cellular metabolism occur in the liquid-filled spaces between these organelles creation of multiple reaction compartments 2. The organelles help to create and maintain optimum conditions (e.g. pH, cofactor/substrate availability, etc.) for the diverse enzymatic reactions creation of a so-called micro-environment 3. Organelles also assure that constructive or anabolic reactions occur at different cellular locations than degradative or catabolic processes separation of anabolism and catabolism 4. Organelles greatly increase the cells internal surface to facilitate multiple places for thousands of chemical reactions happening at the same time increase of the surface-to-volume ration (SVR) 25