2) The Cytoplasm les 2.pptx

Cellen: structurele eenheden van levende organismen Indeling: Prokaryote cellen vs. Eukaryote cellen Prokaryote cellen: bacteria Klein (1-5micrometer lang) Celwand Geen nucleaire enveloppe voor de scheiding van het DNA van de rest van de cel ( DNA zit los in cytoplasma) Geen membranaire structuren ( weinig orde ) Geen histonen gebonden op het DNA Eukaryote cellen Groter ( schimmels planten dieren ) Goed te onderscheiden kern omgeven door een nucleaire enveloppe Histonen in de DNA structuur Verschillende door membranen omgeven organellen ( verschillende compartimenten) CELLULAIRE DIFFERENTIATIE 200 verschillende soorten cellen uit een zygote (oöcyt + spermatozoïde) Differentiatie: synthese van specifieke proteïnen, vorm verandering, specialisatie cfr spiercel. CELLULAIRE DIFFERENTIATIE Belangrijke cellulaire functies door gespecialiseerde cellen zijn opgelijst in tabel 2-1 Functie Gespecialiseerde cel Beweging Spiercel Synthese en secretie van enzymes Acinaire pancreas cel Synthese en secretie van slijm Muceuse cel Synthese en secretie Steroïden bijnier, teelballen, eierstokken Ionentransport nier, speekselklieren Intracellulaire vertering macrofagen Transformeren van fysische en chemische stimuli in zenuw impulsen zintuigcellen darm CELLULAIRE DIFFERENTIATIE Cel ecologie Eigenschappen en gedrag van cellen van hetzelfde type kunnen verschillen ifv het regio en omstandigheden: Bv. macrofagen schakelen over van oxidatief metabolisme naar glycolyse wanneer ze aankomen in ontstekingsweefsel Bv. fibroblasten in borstweefsel en uterus gladde spiercellen zijn veel gevoeliger voor vrouwelijke geslachtshormonen door de aanwezigheid van een specifiek receptorpatroon. CEL COMPONENTEN Basiscomponenten: cytoplasma en de nucleus Cytoplasma Buitenste component: plasmamembraan of plasmalemma Verbinding van het binnenste van de cel (cytoskelet zorgt voor stevigheid ) met extracellulaire macromolecules door integrines Cytoplasma bestaat uit cytosol (vloeibare basissubstantie) met daarin organellen, een cytoskelet en afzettingen van koolhydraten, lipiden en pigmenten. Membranen verdelen de cel in compartimenten met ionentransport, moleculentransport, concentratie van enzymes, eiwitten… De plasmamembraan Componenten: fosfolipiden, cholesterol, proteïnen, oligosacchariden met die componenten moeten we die membraan maken Functies: -selectieve barriére, facilitatie van specifiek transport -=> constant intracellulair milieu -specifieke herkenning Dikte van 7.5 tot 10 nm, trilaminaire structuur (figuur 2-1), de eenheidsmembraan (figuur 2-2) Figure 2–1. The ultrastructure and molecular organization (right) of the cell membrane. The dark lines at left represent the two dense layers observed in the electron microscope; these are caused by the deposit of osmium in the hydrophilic portions of the phospholipid molecules. Figure 2–2. Electron micrograph of a section of the surface of an epithelial cell, showing the unit membrane with its two dark lines enclosing a clear band. The granular material on the surface of the membrane is the glycocalyx. x100,000. • Figure 2–3. A: The fluid mosaic model of membrane structure. The membrane consists of a phospholipid double layer with proteins inserted in it (integral proteins) or bound to the cytoplasmic surface (peripheral proteins). Integral membrane proteins are firmly embedded in the lipid layers. Some of these proteins completely span the bilayer and are called transmembrane proteins, whereas others are embedded in either the outer or inner leaflet of the lipid bilayer. The dotted line in the integral membrane protein is the region where hydrophobic amino acids interact with the hydrophobic portions of the membrane. Many of the proteins and lipids have externally exposed oligosaccharide chains. B: Membrane cleavage occurs when a cell is frozen and fractured (cryofracture). Most of the membrane particles (1) are proteins or aggregates of proteins that remain attached to the half of the membrane adjacent to the cytoplasm (P, or protoplasmic, face of the membrane). Fewer particles are found attached to the outer half of the membrane (E, or extracellular, face). For every protein particle that bulges on one surface, a corresponding depression (2) appears in the opposite surface. Membrane splitting occurs along the line of weakness formed by the fatty acid tails of membrane phospholipids, since only weak hydrophobic interactions bind the halves of the membrane along this line. (Modified and reproduced, with permission, from Krstíc RV: Ultrastructure of the Mammalian Cell. Springer-Verlag, 1979.) Membrane proteins. Both protein and lipid components often have covalently attached oligosaccharide chains exposed at the external membrane surface. These contribute to the cell’s glycocalyx, which provides important antigenic and functional properties to the cell surface. Membrane proteins serve as receptors for various signals coming from outside cells, as parts of intercellular connections, and as selective gateways for molecules entering the cell. Transmembrane proteins often have multiple hydrophobic regions buried within the lipid bilayer to produce a channel or other active site for specific transfer of substances through the membrane. Fosfolipiden=2 lange hydrofobe ketens (staarten) gebonden aan een polair (hydrofiel) hoofd. Dubbellaag = energetisch gunstigste oplossing Cholesterol: verstoring van de dichte pakking van de fosfolipiden, verhoogt de vloeibaarheid van de membraan (# cholesterol ifv vloeibaarheid). De lipiden componenten binnenzijde ≠ buitenzijde; glycolipiden aan de buitenzijde (Figuur 2-3A, 2-4). Glycolipiden spelen een rol bij receptors, cel adhesie… Figure 2–4. Schematic drawing of the molecular structure of the plasma membrane. Note the one-pass and multipass transmembrane proteins. The drawing shows a peripheral protein in the external face of the membrane, but the proteins are present mainly in the cytoplasmic face, as shown in Figure 2–3. (Redrawn and reproduced, with permission, from Junqueira LC, Carneiro J: Biologia Celular e Molecular, 6th ed. Editora Guanabara, 1997.) Proteïnen maken tot 50% van het gewicht uit van de membraan: Integrale proteïnen (soms transmembranair) vs Perifere proteïnen. Integrale eiwitten kunnen de membraan meerdere keren overspannen (Figuur 2-4). Proteïnen zijn ook ongelijk verdeeld over de membraan Integratie van proteïnen in de lipiden door hydrofobe interacties ts. Lipiden en hydrofobe AZ. Itt tot lipiden worden proteïnen in hun laterale diffusie gehinderd door binding op het cytoskelet (2-5). Membraan mozaïek model Figure 2–5. Experiment demonstrating the fluid nature of proteins within the cell membrane. The plasmalemma is shown as 2 parallel lines (representing the lipid portion) in which proteins are embedded. In this experiment, 2 types of cells derived from tissue cultures (one with a fluorescent marker [right] and one without) are fused (A —>B) through the action of the Sendai virus. Minutes after the fusion of the membranes, the fluorescent marker of the labeled cell spreads to the entire surface of the fused cells (C). However, in many cells, most transmembrane proteins are stabilized in place by anchoring to the cytoskeleton. Membraan eiwitten worden aangemaakt in het RER, verder afgewerkt in het GC en via transportvesikels naar het celoppervlak gebracht (2-6). Figure 2–6. The proteins of the plasmalemma are synthesized in the rough endoplasmic reticulum and then transported in vesicles to the Golgi complex, where they may be modified and transferred to the cell membrane. This example shows the synthesis and transport of a glycoprotein, which is an integral protein of the membrane. (Redrawn and reproduced, with permission, from Junqueira LC, Carneiro J: Biologia Celular e Molecular, 6th ed. Editora Guanabara, 1997. Figure 2–5. Formation and maturation of cell membrane proteins. Membrane proteins of the plasmalemma are synthesized in the rough endoplasmic reticulum and then move in transport vesicles to a Golgi apparatus, another cytoplasmic structure with several flattened membrane saccules or cisternae. While in the Golgi apparatus, the oligosaccharide chains are added (glycosylation) to many membrane proteins by enzymes in the Golgi saccules. When glycosylation and other posttranslational modifications are complete, the mature membrane proteins are isolated within vesicles that leave the Golgi apparatus. These vesicles move to the cell membrane and fuse with it, thus incorporating the new membrane proteins (along with the lipid bilayer of the vesicle) into the cell membrane. Glycocalyx = wazige zone naast de membraan (2-2), KH op proteïnen of lipiden verbonden met glycoproteïnen en proteoglycanen (mucus). Figure 2–2. Electron micrograph of a section of the surface of an epithelial cell, showing the unit membrane with its two dark lines enclosing a clear band. The granular material on the surface of the membrane is the glycocalyx. x100,000. Figure 15–28. Cells covering the villi. (a): The columnar epithelium that covers intestinal villi consists mainly of the tall absorptive enterocytes (E). The apical ends of these cells are joined and covered by a brush border of microvilli. Covered by a coating of glycoproteins, the brush border, along with the mucus—secreting goblet cells (G), stains with carbohydrate staining methods. Other cells of the epithelium are scattered enteroendocrine cells, which are difficult to identify in routine preparations, and various immune cells such as intraepithelial lymphocytes. The small spherical nuclei of lymphocytes can be seen between the enterocytes. X200. PAS—hematoxylin. (b): At higher magnification individual microvilli of enterocytes are better seen and the striated appearance of the border is apparent. (c): TEM shows microvilli and densely packed mitochondria of enterocytes, and enteroendocrine cells (EC) with secretory granules can be distinguished along the basal lamina. X1850. Transport Actief transport (Na+, K+, Ca2+) via integrale membraan proteïnes met verbruik van ATP Gefaciliteerde diffusie:Specifiek transporter, symporter, antiporter Zijn coformatieveranderingen Kanaalproteïnes Diffusie Endocytose Vloeistof pinocytose (4-25): fusie van vesikel met lysosoom Receptor gemediëerde endocytose (2-7) – Clatrine eiwitten – endosomen (ATP – protonen pomp) (2-8) Fagocytose cfr macrofagen Exocytose: bv. secretie van granula (4-27): fusogene proteïnen en Ca2+ , vesikel wordt deel van de membraan (membrane trafficking) Figure 2–6. Three major forms of endocytosis. Endocytosis is a process in which a cell takes in material from the extracellular fluid using dynamic movements and fusion of the cell membrane to form cytoplasmic, membrane—enclosed structures containing the material. Such cytoplasmic structures formed during endocytosis fall into the general category of vesicles or vacuoles. (a): Phagocytosis involves the extension from the cell of large folds called pseudopodia which engulf particles, for example bacteria, and then internalize this material into a cytoplasmic vacuole or phagosome. (b): In pinocytosis the cell membrane invaginates (dimples inward) to form a pit containing a drop of extracellular fluid. The pit pinches off inside the cell when the cell membrane fuses and forms a pinocytotic vesicle containing the fluid. (c): Receptor—mediated endocytosis includes membrane proteins called receptors which bind specific molecules (ligands). When many such receptors are bound by their ligands, they aggregate in one membrane region which then invaginates and pinches off to create vesicle or endosome containing both the receptors and the bound ligands. Figure 4—25. Diagram of the ultrastructure of a proximal convoluted tubule cell of the kidney. Invaginations of the basal cell membrane outline regions filled with elongated mitochondria. This typical disposition is present in ion-transporting cells. Interdigitations from neighboring cells interlock with those of this cell. Protein being absorbed from the lumen by pinocytosis is digested by lysosomes. Sodium ions diffuse passively through the apical membranes of these cells. These ions are then actively transported out of the cells by Na+/K+-ATPase located in the basolateral membranes of the cells. Energy for this sodium pump is supplied by nearby mitochondria. Figure 2–7. Schematic representation of the endocytic pathway and membrane trafficking. Ligands, such as hormones and growth factors, bind to specific surface receptors and are internalized in pinocytotic vesicles coated with clathrin and other proteins. After the liberation of the coating molecules, the pinocytotic vesicles fuse with the endosomal compartment, where the low pH causes the separation of the ligands from their receptors. Membrane with receptors is returned to the cell surface to be reused. The ligands typically are transferred to lysosomes. The cytoskeleton with motor proteins is responsible for all vesicle movements described Figure 2–8. Internalization of low-density lipoproteins (LDL) is important to keep the concentration of LDL in body fluids low. LDL, which is rich in cholesterol, binds with high affinity to its receptors in the cell membranes. This binding activates the formation of pinocytotic vesicles from coated pits. The vesicles soon lose their coating, which is returned to the inner surface of the plasmalemma: the uncoated vesicles fuse with endosomes. In the next step, the LDL is transferred to lysosomes for digestion and separation of their components to be utilized by the cell. Figure 4—27. Diagram of a serous (pancreatic acinar) cell. Note its evident polarity, with abundant rough endoplasmic reticulum in the basal region and the Golgi complex and zymogen granules are in the apical region. To the right is a scale indicating the approximate time necessary for each step of synthesis and secretion. Exocytose Ontvangst van signalen Gap junctions Endocrine signaalmolecules (hormonen) -->Naar de bloedbaan Paracrine signaalmolecules ( cel die aan andere cellen iets wilt vertellen) Synaptische overdracht Elke cel heeft een bepaalde mix van receptor moleculen (2-9)  Ontvangst van signalen Hydrofobe signaalmolecules (receptor molecules in de cel – complex naar de kern) Hydrofiele signaalmolecules (membraan receptor) (2-10). Figure 2–10. Diagram illustrating how G proteins switch effectors on and off. (Modified and reprinted, with permission, from Linder M, Gilman AG: G proteins. Sci Am 1992;267:56. Figure 2–10. G proteins and initiation of signal transduction. When a hormone or other signal binds to a membrane receptor, the hormone can begin to cause changes in the cell’s activities after a signal transduction process initiated by the bound receptor. The first step in receptor signaling often involves G proteins which bind guanosine diphosphate (GDP) when inactive and are activated when GDP is exchanged for GTP. A simplified version of G protein activity is shown here. Conformational changes occur in the receptor when it binds its ligand and the changed receptor activates the G protein–GDP complex. A GDP—GTP exchange releases the α subunit of the G protein, which then moves laterally to bind with a transmembrane effector protein, activating it to propagate the signal further by various mechanisms. The α subunit GTP is rapidly converted back to GDP, allowing the polypeptide to reassociate with the rest of the G protein complex, ready Major types of membrane receptors. Protein and most small ligands are hydrophilic molecules that bind transmembrane protein receptors to initiate changes in the target cell. (a) Channel-linked receptors bind ligands such as neurotransmitters and open to allow influx of specific ions. (b) Enzymatic receptors are usually protein kinases that are activated to phosphorylate (and usually activate) other proteins upon ligand binding. (c) G-protein–coupled receptors bind ligand, changing the conformation of its G-protein subunit, allowing it to bind GTP, and activating and releasing this protein to in turn activate other proteins such as ion channels and adenyl cyclase. Ontvangst van signalen: adenyl cyclase/adenylate cyclase c-AMP bindingsproteins => transcription factors, c-AMP dependent kinases, ion transporters Ontvangst van signalen Tabel 2-2 Stimulus Cel G-prot Effector Effect Adrenaline, glucagon Levercel Gs Adenylyl cyclase Afbraak van glycogeen Adrenaline, glucagon Adipocyt Gs Adenylyl cyclase Afbraak van vet Luteinizerend hormoon Eierstokken Gs Adenylyl cyclase Estrogeen, progesteron ADH Nier Gs Adenylyl cyclase Waterretentie Acetylcholine Hartspier Gj Kalium kanaal Daling HF Enkefalines, endorfines, opioïden Neuronen van de hersenen Gj/Go Calcium kanaal, kalium kanaal, verandering electrische activiteit neuronen Adenylyl cyclase Geuren Neuroepitheel cellen in de neus Golf Herkennen van geuren Adenylyl cyclase Mitochondria Sfeervormige – draadvormige organellen (2-11), (2-12). Figure 2–11. Photomicrograph of the stomach inner covering. The large cells show many round and elongated mitochondria in the cytoplasm. The central nuclei are also clearly seen. High magnification. Mitochondria in the light microscope. (a): In sectioned cells stained with H&E, such as certain cells of the stomach inner lining, mitochondria typically appear as numerous eosinophilic structures throughout the cytoplasm. The mitochondria usually appear round or slightly elongated and are more numerous in cytoplasmic regions with higher energy demands, such as near the cell membrane in cells undergoing much active transport. The central nuclei are also clearly seen in these cells. (b): Entire mitochondria can be shown in cultured cells, such as the endothelial cells shown here and often appear as the elongated structures (shown in yellow or orange here), usually arrayed in parallel along microtubules. These preparations along with TEM studies indicate that the elongated shape is typical of mitochondria and that their shape can be quite plastic and variable. Specific mitochondrial staining such as that shown here involves incubating living cells with specific fluorescent compounds that are specifically sequestered into these organelles, followed by fixation and immunocytochemical staining of the microtubules. In this preparation, microtubules are stained green and mitochondria appear yellow or orange, depending on their association with the green microtubules. The cell nucleus was stained with DAPI. (Figure 2–11b, with permission, from Invitrogen.) Mitochondria in the light microscope. (a)In certain sectioned cells stained with H&E, mitochondria appear throughout the cytoplasm as numerous eosinophilic structures. The mitochondria usually appear round or slightly elongated and are more numerous in cytoplasmic regions with higher energy demands, such as near the cell membrane in cells undergoing much active transport. The central nuclei are also clearly seen in these cells. (b)The distribution and morphology of mitochondria (yellow/green) can be shown here with intact cultured epithelial cells. Mitochondria are most abundant near cell nuclei (blue), reflecting the greater need for ATP in the synthetic activities within that region. Such preparations also show that mitochondrial shape can be quite plastic and variable. The length of these organelles, while usually only a few times their diameters, can be greatly elongated as shown here. Such mitochondria tend to be oriented along microtubules (not visualized here). (Figure 2–19b, reproduced with permission from The Human Protein Atlas project.) Figure 2–12. Mitochondria. The two mitochondrial membranes and central matrix can be seen here in the diagram and the TEM. The outer membrane is smooth and the inner membrane, shown at left, has many sharp folds called cristae which increase its surface area greatly. Cristae are most numerous in mitochondria of highly active cells. The matrix is a gel containing numerous enzymes. The inner membrane surface in contact with the matrix is studded with many multimeric protein complexes resembling globular units on short stalks. These contain the ATP synthase complexes that generate most of the cell’s ATP. Figure 2–12. Three-dimensional representation of a mitochondrion with its cristae penetrating the matrix space. Note that 2 membranes delimiting an intermembrane space form the wall of the mitochondrion. The cristae are covered with globular units that participate in the formation of ATP. Locatie in de cel ifv energieverbruik (17-3) (21-10) (4-25) Figure 17—3. Electron micrograph of ciliated columnar cells of the respiratory epithelium, showing the ciliary microtubules in transverse and oblique section. In the cell apex are the U-shaped basal bodies that serve as the source of, and anchoring sites for, the ciliary axonemes. The local accumulation of mitochondria is related to energy production for ciliary movement. Note the junctional complex. x9200. Figure 16–16. Ultrastructure of hepatocytes and bile canaliculi. (a): TEM of hepatocytes show small bile canaliculi (BC) between two cells, with junctional complexes binding the cells firmly and tightly at these sites. The bile canaliculus is the site of exocrine secretion by hepatocytes. The two adjoining hepatocytes extend short microvilli and secrete bile components into this space. The hepatocytes have many mitochondria (M), small electron—dense glycogen granules, and Golgi complexes (G) and extend more numerous microvilli into the perisinusoidal space (PS), which is the site where hepatocytes remove and add components in plasma. The endothelial cell (E) lining the sinusoid (S) is also seen. X9500. (b): SEM of hepatocytes (H) broken apart from one another reveals the length of a bile canaliculus (BC) along the cell’s surface. Such canaliculi run between the cells of the hepatocyte plates in the hepatic lobules and carry bile toward the portal areas where the canaliculi join cuboidal bile ductules. (Figure 16–16a, with permission, from Douglas L. Schmucker, Department of Anatomy, University of California, San Francisco.) Figure 19–10. Ultrastructure of proximal convoluted tubule cells. TEM reveals important features of the cuboidal cells of the proximal convoluted epithelium: the long, dense apical microvilli (MV), the abundant pinocytotic pits and vesicles (V) in the apical regions near lysosomes (L). Small proteins brought into the cells nonspecifically by pinocytosis are degraded in lysosomes and the amino acids released basally. Apical ends of adjacent cells are sealed with zonula occludens, but the basolateral sides are characterized by long invaginating folds of membrane along which many long mitochondria (M) are situated. These folds provide a greatly increased surface area for pumping of ions across the membrane. Water and the small molecules released from the proximal convoluted tubules are taken up immediately by the adjacent peritubular capillaries (C). Between the basement membranes of the tubule and the capillary shown here is an extension of a fibroblast (F). X10,500. Figure 16–21. Gallbladder. The gallbladder is a saclike structure that stores and concentrates bile, and releases it into the duodenum after a meal. (a): Its wall consists largely of a highly folded mucosa, with a simple columnar epithelium (arrows) overlying a typical lamina propria (LP); a muscularis (M) with bundles of muscle fibers oriented in all directions to facilitate emptying of the organ; an external adventitia (A) where it is against the liver and a serosa where it is exposed. X60. H&E. (b): TEM of the epithelium shows cells specialized for water uptake across apical microvilli (MV) and release into the intercellular spaces (arrows) along the folded basolateral cell membranes. Abundant mitochondria provide the energy for this pumping process. Scattered apical secretory granules (G) contain mucus. X5600. Figure 21—10. Top: The principal changes occurring in spermatids during spermiogenesis. The basic structural feature of the spermatozoon is the head, which consists primarily of condensed nuclear chromatin. The reduced volume of the nucleus affords the sperm greater mobility and may protect the genome from damage while in transit to the egg. The rest of the spermatozoon is structurally arranged to promote motility. Bottom: The structure of a mature spermatozoon. Figure 4—25. Diagram of the ultrastructure of a proximal convoluted tubule cell of the kidney. Invaginations of the basal cell membrane outline regions filled with elongated mitochondria. This typical disposition is present in ion-transporting cells. Interdigitations from neighboring cells interlock with those of this cell. Protein being absorbed from the lumen by pinocytosis is digested by lysosomes. Sodium ions diffuse passively through the apical membranes of these cells. These ions are then actively transported out of the cells by Na+/K+-ATPase located in the basolateral membranes of the cells. Energy for this sodium pump is supplied by nearby mitochondria. Productie van ATP (energierijke molecule): nodig voor osmotische, mechanische, elektrische of chemische arbeid. Structuur (2-12), (2-13A): buitenste en binnenste membraan, tussenruimte, matrix, cristae. Figure 2–12. Three-dimensional representation of a mitochondrion with its cristae penetrating the matrix space. Note that 2 membranes delimiting an intermembrane space form the wall of the mitochondrion. The cristae are covered with globular units that participate in the formation of ATP. Figure 2–13. Structural lability of mitochondria. A: Electron micrograph of a section of rat pancreas. A mitochondrion with its membranes, cristae (C), and matrix (M) is seen in the center. Numerous flattened cisternae of rough endoplasmic reticulum (RER) with ribosomes on their cytoplasmic surfaces are also visible. x50,000. B: Electron micrograph of striated muscle from a patient with mitochondrial myopathy. The mitochondria are profoundly modified, showing marked swelling of the matrix. Tubulaire cristae (4-36). Figure 4—36. Diagram of the ultrastructure of a hypothetical steroid-secreting cell. Note the abundance of the smooth endoplasmic reticulum (SER), lipid droplets, Golgi complex, and lysosomes. The numerous mitochondria have mainly tubular cristae. They not only produce the energy necessary for the activity of the cell but are also involved in steroid hormone synthesis. Rough endoplasmic reticulum (RER) is also shown. Krebscyclus – ß-oxidatie– oxidatieve fosforylering – electronentransport ATP productie op basis van een chemi-osmotische gradient Aantal mitochondria en aantal cristae ifv de energiebehoefte van de cel Circulair DNA en RNA in de matrix ( veel cristae  veel energie) Proteïnen aanmaak op basis van DNAm en DNAn (import op basis van signaalsequentie) Anaërobe afbraak van glucose (cytosol 2-ATP) versus aërobe (mitochondrion 36-ATP) Mitochondria groeien en delen door splitsing( prokaryote eigenschap) Tijdens de celdeling (mitose) krijgt elke dochtercel ongeveer ½ van de mitochondria Endosymbiose Mitochondrial structure and ATP formation (Legend Opposite). (a)The two mitochondrial membranes and the innermost matrix can be seen in the TEM and diagram. The outer membrane is smooth and the inner membrane has many sharp folds called cristae that increase its surface area greatly. The matrix is a gel with a high concentration of enzymes. (b)Metabolites such as pyruvate and fatty acids enter mitochondria via membrane porins and are converted to acetyl CoA by matrix enzymes of the citric acid cycle (or Krebs cycle), yielding some ATP and NADH (nicotinamide adenine dinucleotide), a major source of electrons for the electron-transport chain. The movement of electrons through the protein complexes of the inner membrane’s electron-transport system is accompanied by the directed movement of protons (H+) from the matrix into the intermembranous space, producing an electrochemical gradient across the membrane. Other membrane-associated proteins make up the ATP synthase systems, each of which forms a globular complex on a stalk-like structure projecting from the matrix side of the inner membrane. A channel in this enzyme complex allows proton flow down the electrochemical gradient and across the membrane back into the matrix. The flow of protons causes rapid spinning of specific polypeptides in the globular ATP synthase complex, converting the energy of proton flow into mechanical energy, which other subunit proteins store in the new phosphate bond of ATP. FIGURE 17.3 Cellular respiration. The citric acid cycle constitutes the first stage in cellular respiration, the removal of high-energy electrons from carbon fuels in the form of NADH and FADH2 (blue pathway). These electrons reduce O2 to generate a proton gradient (red pathway), which is used to synthesize ATP (green pathway). The reduction of O2 and the synthesis of ATP constitute oxidative phosphorylation. Figure 2–14. The chemiosmotic theory of mitochondrial energy transduction. Middle: The flux of protons is directed from the matrix to the intermembranous space promoted at the expense of energy derived from the electron transport system in the inner membrane. Left: Half the energy derived from proton reflux produces ATP; the remaining energy produces heat. Right: The protein thermogenin, present in multilocular adipose tissue, forms a shunt for reflux of protons. This reflux, which dissipates energy as heat, does not produce ATP (see Chapter 6). Ribosomen Prokaryote >< eukaryote ribosomen Eukaryote ribosomen: synthese in de nucleus met inbouw van eiwitten uit het cytoplasma – nuclear pores Basofiel (veel fosfaatgroepen) Polyribosomen (2-15A) in het cytoplasma of op het ER (2-15B) Figure 2–15. Diagram illustrating (A) the concept that cells synthesizing proteins (represented here by spirals) that are to remain within the cytoplasm possess (free) polyribosomes (ie, nonadherent to the endoplasmic reticulum). In B, where the proteins are segregated in the endoplasmic reticulum and may eventually be extruded from the cytoplasm (export proteins), not only do the polyribosomes adhere to the membranes of rough endoplasmic reticulum, but the proteins produced by them are injected into the interior of the organelle across its membrane. In this way, the proteins, especially enzymes such as ribonucleases and proteases, which could have undesirable effects on the cytoplasm, are separated from it. Polyribosomes: free or bound to the endoplasmic reticulum. Free polyribosomes (not attached to the endoplasmic reticulum, or ER) synthesize cytosolic and cytoskeletal proteins and proteins for import into the nucleus, mitochondria, and peroxisomes. Proteins that are to be incorporated into membranes, stored in lysosomes, or eventually secreted from the cell are made on polysomes attached to the membranes of ER. The proteins produced by these ribosomes are segregated during translation into the interior of the ER’s membrane cisternae. In both pathways, misfolded proteins are conjugated to ubiquitin and targeted for proteasomal degradation. Endoplasmatisch reticulum Anastosmoserend netwerk van kanalen en blaasjes – cisternen - (2-16) – continue verbinding! Figure 2–16. The endoplasmic reticulum is an anastomosing network of intercommunicating channels and sacs formed by a continuous membrane. Note that the smooth endoplasmic reticulum (foreground) is devoid of ribosomes, the small dark dots that are present in the rough endoplasmic reticulum (background). The cisternae of the smooth reticulum are tubular, whereas in the rough reticulum they are flat sacs. Rough and smooth endoplasmic reticulum. (a)The endoplasmic reticulum is an anastomosing network of intercommunicating channels or cisternae formed by a continuous membrane, with some regions that bear polysomes appearing rough and other regions appearing smooth. While RER is the site for synthesis of most membrane-bound proteins, three diverse activities are associated with smooth ER: (1) lipid biosynthesis, (2) detoxification of potentially harmful compounds, and (3) sequestration of Ca+ + ions. Specific cell types with well-developed SER are usually specialized for one of these functions. (b)By TEM cisternae of RER appear separated, but they actually form a continuous channel or compartment in the cytoplasm. The interconnected membranous cisternae of RER are flattened, while those of SER are frequently tubular. (14,000X) (c)Here, with fluorescence microscopy and immunocytochemistry of intact epithelial cells in culture, the lacelike ER (yellow/green) is shown to be continuous with the nuclear envelope and most abundant in the surrounding area, but present throughout the cytoplasm. ER was visualized with a fluorescently tagged antibody against an enzyme specific to that organelle. Cell nuclei are stained bright blue with DAPI (4’,6-diamidino-2-phenylindole) and microtubules red with a fluorescent antibody against tubulin. (Figure 2–10c Reproduced with permission from The Human Protein Atlas project.) RER Proteïnsecretie (2-13) (2-17) In contact met de nucleaire enveloppe Ruw door ribosomen Scheiden van proteïnen van het cytosol, glycolisatie van glycoproteinen, synthese van fosfolipiden, secundaire en tertaire aanpassingen, assembleren van quaternaire structuren, posttranslationele modificaties Proteïn synthese start in het cytosol – signaal sequentie (2-18) Bestemmingen: intracellulair, tijdelijke stapeling, onderdeel van de membraan (2-19). Figure 2–13. Structural lability of mitochondria. A: Electron micrograph of a section of rat pancreas. A mitochondrion with its membranes, cristae (C), and matrix (M) is seen in the center. Numerous flattened cisternae of rough endoplasmic reticulum (RER) with ribosomes on their cytoplasmic surfaces are also visible. x50,000. B: Electron micrograph of striated muscle from a patient with mitochondrial myopathy. The mitochondria are profoundly modified, showing marked swelling of the matrix. Figure 2–17. Schematic representation of a small portion of the rough endoplasmic reticulum to show the shape of its cisternae and the presence of numerous ribosomes which are part of polyribosomes. It should be kept in mind that the cisternae appear separated in sections made for electron microscopy, but they form a continuous tunnel in the cytoplasm. Figure 2–18. The transport of proteins across the membrane of the rough endoplasmic reticulum (RER). The ribosomes bind to mRNA, and the signal peptide is initially bound to a signal-recognition particle (SRP). Ribosomes bind to the RER by interacting with the SRP and a ribosomal receptor. The signal peptide is then removed by a signal peptidase (not shown). These interactions cause the opening of a pore through which the protein is extruded into the RER. Movement of polypeptides into the RER. The newly translated amino terminus of a protein to be incorporated into membranes or sequestered into vesicles contains 15-40 amino acids that include a specific sequence of hydrophobic residues comprising the signal sequence or signal peptide. This sequence is bound by a signal-recognition particle (SRP), which then recognizes and binds a receptor on the ER. Another receptor in the ER membrane binds a structural protein of the large ribosomal subunit, more firmly attaching the ribosome to the ER. The hydrophobic signal peptide is translocated through a protein pore (translocon) in the ER membrane, and the SRP is freed for reuse. The signal peptide is removed from the growing protein by a peptidase and translocation of the growing polypeptide continues until it is completely segregated into the ER cisterna. Protein localization and cell morphology. The ultrastructure and general histologic appearance of a cell are determined by the nature of the most prominent proteins the cell is making. (a) Cells that make few or no proteins for secretion have very little RER, with essentially all polyribosomes free in the cytoplasm. (b)Cells that synthesize, segregate, and store various proteins in specific secretory granules or vesicles always have RER, a Golgi apparatus, and a supply of granules containing the proteins ready to be secreted. (c)Cells with extensive RER and a well-developed Golgi apparatus show few secretory granules because the proteins undergo exocytosis immediately after Golgi processing is complete. Many cells, especially those of epithelia, are polarized, meaning that the distribution of RER and secretory vesicles is different in various regions or poles of the cell. (d)Epithelial cells specialized for secretion have distinct polarity, with RER abundant at their basal ends and mature secretory granules at the apical poles undergoing exocytosis into an enclosed extracellular compartment, the lumen of a gland. Figure 16–10. Pancreatic acinar cells. TEM of a pancreatic acinar cell shows its pyramidal shape and the round, basal nucleus (N) surrounded by cytoplasm packed with cisternae of rough ER (RER). The Golgi apparatus (G) is situated at the apical side of the nucleus and is associated with condensing vacuoles (C) and numerous secretory (zymogen) granules (S). The small lumen (L) of the acinus contains proteins recently released from the cell by exocytosis. Exocytosis of digestive enzymes from secretory granules is promoted by CCK, released from the duodenum when food enters that region from the stomach. X8000. Figure 17–16. Ultrastructure of type II alveolar cells. TEM of a type II alveolar cell protruding into the alveolar lumen shows unusual cytoplasmic features. Arrows indicate lamellar bodies which store newly synthesized pulmonary surfactant after processing of its components in rough ER (RER) and the Golgi apparatus (G). Smaller multivesicular bodies with intralumenal vesicles are also often present. Short microvilli are present and the type II cell is attached via junctional complexes (JC) with the adjacent, very thin type I epithelial cell. The ECM contains prominent reticular fibers (RF). X17,000. (Reproduced, with permission from Dr. Mary C. Williams, Pulmonary Center and Department of Anatomy, Boston University School of Medicine.) Figure 17–17. Type II alveolar cell function. Diagram illustrates secretion of surfactant by a type II cell. Surfactant contains protein—lipid complexes synthesized initially in the ER and Golgi, with further processing and storage in large organelles called lamellar bodies. Multivesicular bodies are organelles smaller than most lamellar bodies that are frequently seen in type II alveolar cells. Such bodies form when the membrane components of an early endosome are sorted, invaginate, and pinch off into smaller vesicles inside the endosome’s lumen. Multivesicular bodies interact with Golgi complexes, with some or most intralumenal vesicle components being ubiquinated for degradation while other components and the surrounding membrane are recycled to the cell membrane, or in the case of type II alveolar cells, first added to the content of lamellar bodies. Surfactant is secreted continuously by exocytosis and forms an oily monomolecular film of lipid over an aqueous hypophase containing proteins. Occluding junctions around the margins of the epithelial cells prevent leakage of tissue fluid into the alveolar lumen. SER Geen polyribosomen Meer tubulair, verbonden onregelmatige (naar grootte en vorm) kanalen. Functies: *steroïd synthese (bv in de bijnierschors) (4-36) * oxidatie, conjugatie, methylatie (bv. Detoxificatie in de levercel) * synthese van fosfolipiden waarna verschillende vervoer mogelijkheden - via vesikels (met behulp van motorproteïnes via cytoskelet) - onmiddellijke communicatie met het SER - transfert proteïnen (2-20) Zowel SER en RER in de lever bevatten het enzym glucose-6-fosfatase In de spier is het SER betrokken bij de verdeling en vrijstelling van Ca2+ Figure 4—36. Diagram of the ultrastructure of a hypothetical steroid-secreting cell. Note the abundance of the smooth endoplasmic reticulum (SER), lipid droplets, Golgi complex, and lysosomes. The numerous mitochondria have mainly tubular cristae. They not only produce the energy necessary for the activity of the cell but are also involved in steroid hormone synthesis. Rough endoplasmic reticulum (RER) is also shown. Figure 15–29. Lipid absorption and processing by enterocytes. (a): TEM showing that enterocytes involved in lipid absorption accumulate many small lipid droplets in vesicles of the smooth ER. These vesicles fuse near the nucleus, forming larger globules that are moved laterally and cross the cell membrane to the extracellular space (arrows) for eventual uptake by lymphatic capillaries (lacteals) in the lamina propria. X5000. (b): Diagram explaining how lipids are processed by enterocytes. Bile components in the lumen emulsify fats into lipid droplets, which are broken down further by lipases to monoglycerides and fatty acids. These compounds are stabilized in an emulsion by the action of bile acids. The products of hydrolysis diffuse passively across the microvilli membranes and are collected in the cisternae of the smooth ER, where they are resynthesized as triglycerides. Processed through the RER and Golgi, these triglycerides are surrounded by a thin layer of proteins and packaged in vesicles containing chylomicrons (0.2–1 µm in diameter) of lipid complexed with protein. Chylomicrons are transferred to the lateral cell membrane, secreted by exocytosis, and flow into the extracellular space in the direction of the lamina propria, where most enter the lymph in lacteals. (Figure 15–29a, with permission, from Robert R. Cardell, Jr, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine.) Figure 2–20. Schematic representation of a phospholipid-transporting amphipathic protein. Phospholipid molecules are transported from lipid-rich (SER) to lipid-poor membranes. (Redrawn and reproduced, with permission, from Junqueira LC, Carneiro J: Biologia Celular e Molecular, 6th ed. Editora Guanabara, 1997.) Golgi Complex (Golgi Apparaat) Bestaat uit membranaire cisternae (2-21, 2-22, 2-23). In gepolariseerde cellen (4-31) tussen nucleus en de apicale celmembraan. Polarisatie in het GC – cis (vormende) zijde versus trans (mature) zijde, verschillende enzym inhoud Functie: *vervolledigen van de posttranslationele veranderingen (glycolisatie, sulfateren, fosforyleren, proteolyse) *initiëren van het verpakken, concentreren en stockeren van de producten * adresseren Figure 2–21. Three-dimensional representation of a Golgi complex. Through transport vesicles that fuse with the Golgi cis face, the complex receives several types of molecules produced in the rough endoplasmic reticulum (RER). After Golgi processing, these molecules are released from the Golgi trans face in larger vesicles to constitute secretory vesicles, lysosomes, or other cytoplasmic components. Figure 2–17. Movement of polypeptides into the RER. Proteins to be incorporated into membranes or sequestered into vesicles contain 20 to 25 hydrophobic amino acids comprising the signal sequence or signal peptide in the regionFigure 2–20. Golgi apparatus. The Golgi apparatus is a highly plastic, morphologically complex system of membrane vesicles and cisternae in which proteins and other molecules made in the ER undergo modification and maturation and then are sorted into specific vesicles destined for different roles in the cell. (a): Transport vesicles emerging from the RER move toward and fuse at the cis, entry, or forming face of the Golgi, merging with the first of several flattened Golgi cisternae. Movement through the Golgi remains a subject of intense investigation, but data suggest that other transport vesicles move proteins serially through the cisternae until at the trans, exit, or maturing face larger vesicles and vacuoles emerge to carry fully modified proteins elsewhere in the cell. Formation and fusion of the vesicles through the Golgi apparatus is controlled by specific membrane proteins. Depending on their protein contents, vesicles are directed toward different regions of the Golgi by specific interactions of these proteins with other membrane proteins. Peripheral membrane proteins important for directed vesicle fusion are the golgins. These are an important Golgi—specific family of proteins, characterized by central coiled— coil domains, which interact with GTPases and many other binding proteins to organize, shape, and specify Golgi membranes. Golgi vesicles may become lysosomes, secretory vesicles that undergo exocytosis, and portions of the plasma membrane. (b): Morphological aspects of the Golgi apparatus are revealed by the SEM, which shows a three— dimensional snapshot of the region between RER and the Golgi membrane compartments. Cells may have multiple Golgi apparatuses, each with stacks of cisternae and dynamic cis and trans faces, and these typically are situated near the cell nucleus. This has been shown in careful TEM studies but is also clearly seen in intact cultured cells. (c): The fibroblast was processed by immunocytochemistry using an antibody against golgin—97 to show many complexes of Golgi vesicles (green), all near the nucleus, against a background of microfilaments organized as stress fibers and stained with fluorescent phalloidin (violet). Because of the abundance of lipids in its many membranes, the Golgi apparatus is difficult to visualize by light microscopy in typical paraffin—embedded, H&E stained sections. In cells with very active Golgi complexes however, such as developing white blood cells, the organelle can sometimes be seen as a faint unstained juxtanuclear region (sometimes called a “Golgi ghost”) surrounded by basophilic cytoplasm. (Figure 2–20b reproduced, with permission, from T. Naguro and A. Iino: Prog. Clin. Biol. Res. 1989;295:250. Copyright ©1989 by Wiley—Liss, Inc., a subsidiary of John Wiley & Sons, Inc. Figure 2–20c, with permission, from Invitrogen.) Golgi apparatus. The Golgi apparatus is a highly plastic, morphologically complex system of membrane vesicles and cisternae in which proteins and other molecules made in the RER undergo further modification and sorting into specific vesicles destined for different roles in the cell. (a)TEM of the Golgi apparatus provided early evidence about how this organelle functions. Near the cell nucleus (N) are small portions of electron-dense RER cisternae, adjacent to which is the face of the cisGolgi network (CGN), or the receiving face of the Golgi apparatus, the first of several wide, flattened Golgi cisternae. This adjoins a stack of characteristically flattened and curved medial Golgi cisternae. Cytological and molecular data indicate that transport vesicles (TV) move proteins serially into and through these cisternae until at the trans Golgi network (TGN), the Golgi’s shipping region, such vesicles condense to form larger secretory vesicles (SV) or other vacuoles that emerge to carry their content of modified proteins elsewhere in the cell. Formation, fusion and movement of transport vesicles through the Golgi apparatus is regulated by specific membrane proteins. (X30,000). (b)Morphological aspects of the Golgi apparatus are revealed more clearly by SEM, which shows a three-dimensional image of the Golgi membrane compartments, with numerous transport vesicles and the trans side facing the lower right. Cells may have multiple Golgi apparatuses, each with the general organization shown here and typically situated near the cell nucleus. (X35,000) (c)The Golgi apparatus can be clearly localized in fluorescent microscopy of intact cultured cells processed by immunocytochemistry with a fluorescent antibody against a Golgi-specific protein (Golgi reassembly-stacking protein 1), which shows complexes of Golgi vesicles (green), near cell nuclei (blue, DAPI-stained), against a background of microtubules stained red with a fluorescent antibody against tubulin. This perinuclear location of Golgi complexes and their proximity to RER are characteristic of this organelle. Because of the abundance of lipids in its many membranes, the Golgi apparatus is difficult to visualize in typical paraffin-embedded, H&E-stained sections. In developing white blood cells with active Golgi complexes, the organelle can sometimes appear as a faint unstained juxtanuclear region (sometimes called a “Golgi ghost”) surrounded by basophilic cytoplasm. (Figure 2–13c reproduced with permission from The Human Protein Atlas project.) Figure 2–22. Summary of Golgi apparatus structure and function. Summary of the main events occurring during protein trafficking and sorting from the rough ER through the Golgi complex. Numbered at the left are the main molecular processes that take place in the compartments shown. In the trans Golgi network, the proteins and glycoproteins combine with specific receptors that guide them to the next stages toward their destinations. On the left side of the drawing is the returning flux of membrane, from the Golgi to the endoplasmic reticulum. Figure 2–22. Electron micrograph of a Golgi complex of a mucous cell. To the right is a cisterna (arrow) of the rough endoplasmic reticulum containing granular material. Close to it are small vesicles containing this material. This is the cis face of the complex. In the center are flattened and stacked cisternae of the Golgi complex. Dilatations can be observed extending from the ends of the cisternae. These dilatations gradually detach themselves from the cisternae and fuse, forming the secretory granules (1, 2, and 3). This is the trans face. Near the plasma membrane of two neighboring cells is endoplasmic reticulum with a smooth section (SER) and a rough section (RER). x30,000. Inset: The Golgi complex as seen in 1micrometer sections of epididymis cells impregnated with silver. x1200. Figure 2–23. Main events occurring during trafficking and sorting of proteins through the Golgi complex. Numbered at the left are the main molecular processes that take place in the compartments indicated. Note that the labeling of lysosomal enzymes starts early in the cis Golgi network. In the trans Golgi network, the glycoproteins combine with specific receptors that guide them to their destination. On the left side of the drawing is the returning flux of membrane, from the Golgi to the endoplasmic reticulum. (Redrawn and reproduced, with permission, from Junqueira LC, Carneiro J: Biologia Celular e Molecular, 6th ed. Editora Guanabara, 1997.) Figure 4—31. Diagram of a mucus-secreting intestinal goblet cell showing a typically constricted base, where the nucleus, mitochondria, and rough endoplasmic reticulum (RER) are located. The protein part of the glycoprotein complex is synthesized in the endoplasmic reticulum. A well-developed Golgi complex is present in the supranuclear region. To the right is a scale indicating the approximate time necessary for each step of synthesis and secretion. (Redrawn after Gordon and reproduced, with permission, from Ham AW: Histology, 6th ed. Lippincott, 1969.) Lysosomen Sites van intracellulaire vertering, turn-over van cellulaire componenten (2-24), (2-25), (2-26) Vesikel met meer dan 40 verschillende soorten hydrolytische enzymes (zure fosfatase;ribonuclease, deoxyribonuclease, glucuronidase) pH optimum! Vooral in fagocyterende cellen. Figure 2–24. Photomicrograph of a kidney tubule whose lumen appears in the center as a long slit. The numerous dark-stained cytoplasmic granules are lysosomes (L), organelles abundant in these kidney cells. The cell nuclei (N), some showing a nucleolus, are also seen in the photograph as dark-stained corpuscles. Toluidine blue stain. High magnification. Figure 2–25. Electron micrograph of a macrophage. Note the abundant cytoplasmic extensions (arrows). In the center is a centriole (C) surrounded by Golgi cisternae (G). Secondary lysosomes (L) are abundant. x15,000. Figure 2–26. Electron micrograph showing 4 dark secondary lysosomes surrounded by numerous mitochondria Lysosomen Lysosomiale enzymes geproduceerd in het RER - -> GC -> verpakt als lysosoom (herkenning via oligosaccharides) Primaire lysosomen – secundaire lysosomen – recyclage nutriënten residues (leeftijds pigment) (2-27), (2-28) Autofagosomen Figure 2–27. Current concepts of the functions of lysosomes. Synthesis occurs in the rough endoplasmic reticulum (RER), and the enzymes are packaged in the Golgi complex. Note the heterophagosomes, in which bacteria are being destroyed, and the autophagosomes, with RER and mitochondria in the process of digestion. Heterophagosomes and autophagosomes are secondary lysosomes. The result of their digestion can be excreted, but sometimes the secondary lysosome creates a residual body, containing remnants of undigested molecules. In some cells, such as osteoclasts, the lysosomal enzymes are secreted to the extracellular environment. Nu, nucleolus. Figure 2–25. Lysosomal functions. Synthesis of the digestive enzymes occurs in the rough ER, and the enzymes are packaged in the Golgi apparatus. Heterophagosomes, in which bacteria are being destroyed, are formed by the fusion of the phagosomes and lysosomes. Autophagosomes, such as those depicted here with ER and mitochondria in the process of digestion, are formed after nonfunctional or surplus organelles become enclosed with membrane and the resulting structure fuses with a lysosome. The products of digestion can be excreted from the cell by exocytosis, but may remain in a membrane—enclosed residual body, containing remnants of indigestible molecules. Residual bodies can accumulate in long—lived cells and be visualized as lipofuscin granules. In some cells, such as osteoclasts, the lysosomal enzymes are secreted to a restricted extracellular compartment. Figure 1–10. Enzyme histochemistry. (a): Micrograph of cross sections of kidney tubules treated histochemically by the Gomori method for alkaline phosphatases show strong activity of this enzyme at the apical surfaces of the cells at the lumen of the tubules (arrows). (b): TEM image of a kidney cell in which acid phosphatase has been localized histochemically in three lysosomes (Ly) near the nucleus (N). The dark material within these structures is lead phosphate that precipitated in places with acid phosphatase activity. X25,000. (Figure 1–10b, with permission, from Eduardo Katchburian, Department of Morphology, Federal University of Sao Paulo, Brazil.) Lysosomes. Lysosomes are spherical membrane-enclosed vesicles that function as sites of intracellular digestion and are particularly numerous in cells active after the various types of endocytosis. Lysosomes are not well shown on H&E-stained cells but can be visualized by light microscopy after staining with toluidine blue. (a)Cells in a kidney tubule show numerous purple lysosomes (L) in the cytoplasmic area between the basally located nuclei (N) and apical ends of the cells at the center of the tubule. Using endocytosis, these cells actively take up small proteins in the lumen of the tubule, degrade the proteins in lysosomes, and then release the resulting amino acids for reuse. (X300) 35 (b)The wide distribution of small lysosomes (green) within intact cultured epithelial cells is shown by immunocytochemistry with an antibody against a granulin precursor specific for these organelles. Microtubules (red) are localized through almost the full extent of cytoplasm around the cells’ nuclei (blue). (c)In the TEM, lysosomes (L) have a characteristic very electron-dense appearance and are shown here near groups of Golgi cisternae (G). The less electron-dense lysosomes represent heterolysosomes in which digestion of the contents is under way. The cell is a macrophage with numerous fine cytoplasmic extensions (arrows). (X15,000) (Figure 2–16b, reproduced with permission from The Human Protein Atlas project) Autophagy. Autophagy is a process in which the cell uses lysosomes to dispose of excess or nonfunctioning organelles or membranes. Membrane that appears to emerge from the SER encloses the organelles to be destroyed, forming an autophagosome that then fuses with a lysosome for digestion of the contents. In this TEM the two autophagosomes at the upper left contain portions of RER more electron dense than the neighboring normal RER and one near the center contains what may be mitochondrial membranes plus RER. Also shown is a vesicle with features of a residual body (RB). (30,000X) Proteasomen •Vertering van individuele proteïnen (overschot, imperfecte) •Ubiquitine (76-AZ) markeert versleten proteïnen op lysine ( 1/ 20 ) •ATP-ase zorgen voor het ontvouwen van de proteïnen daarna afbraak Peroxisomen (Microbodies) •Peroxisomen (2-39) oxideren organische substraten: verwijderen van waterstofatomen en transfereren naar O2 met vorming van H2O2. •Catalase: verwijdering van H2O2, detoxificatie (bv ethylalcohol) •Eiwitten/enzymes gesynthetiseerd op vrije polyribosomen i.t.t. Lysosoom! Figure 2–39. Electron micrograph of a section of a liver cell showing glycogen deposits as accumulations of electron-dense particles (arrows). The dark structures with a dense core are peroxisomes. Mitochondria (M) are also shown. x30,000 Peroxisomes. Peroxisomes are small spherical, membranous organelles, containing enzymes that use O2 to remove hydrogen atoms from fatty acids, in a reaction that produces hydrogen peroxide (H2O2) that must be broken down to water and O2 by another enzyme, catalase. (a) By TEM peroxisomes (P) generally show a matrix of moderate electron density. Aggregated electron-dense particles represent glycogen (G). (X30,000) (b)Peroxisomes (P) in most species are characterized by a central, more electron-dense crystalloid aggregate of constituent enzymes, as shown here. (X60,000) (c)The small size, large number, and widespread cellular distribution of peroxisomes (green) is shown in cultured osteosarcoma cells processed for immunocytochemistry with a fluorescent antibody against a protein specific to this organelle. Cell nuclei are stained bright blue with DAPI. (Figure 2–21c reproduced with permission from The Human Protein Atlas project.) HET CYTOSKELET Netwerk van MT, MF(actine filamenten), IF Structurele eiwitten zorgen voor vorm en beweging (van vesikels en organellen, van de cel) Microtubules and actin filaments in cytoplasm. (a)Microtubules (MT) and actin microfilaments (MF) can both be clearly distinguished in this TEM of fibroblast cytoplasm, which provides a good comparison of the relative diameters of these two cytoskeletal components. (X60,000) (b)Arrays of microfilaments and microtubules are easily demonstrated by immunocytochemistry using antibodies against their subunit proteins, as in this cultured cell. Actin filaments (red) are most concentrated at the cell periphery, forming prominent circumferential bundles from which finer filaments project into cellular extensions and push against the cell membrane. Actin filaments form a dynamic network important for cell shape changes such as those during cell division, locomotion, and formation of cellular processes, folds, pseudopodia, lamellipodia, microvilli, etc, which serve to change a cell’s surface area or give direction to a cell’s crawling movements. Microtubules (green/yellow) are oriented in arrays that generally extend from the centrosome area near the nucleus into the most peripheral exten

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