Cell Structure 2 - Cell Biology 3 PDF

10/9/24 Cell Structure 2 Cell Biology 3 1 Power plan ENDOMEMBRANE SYSTEM HEADQUATER ER Nucleus Golgi 01 0...

10/9/24 Cell Structure 2 Cell Biology 3 1 Power plan ENDOMEMBRANE SYSTEM HEADQUATER ER Nucleus Golgi 01 04 Endosome DIGESTION CENTER 02 03 POWER PLAN Lysosome Mitochondria Peroxisome Chloroplast Vacuole 2 1  10/9/24 LEARNING OBJECTIVES Characteristics of mitochondria - Mitochondrial ATP synthesis - Mitochondrial biogenesis Characteristics of peroxisomes Characteristics of lysosomes Characteristics of proteasomes and the role of ubiquitin Components of the cytoskeleton - Microtubules - Actin filaments - Intermediate filaments - Molecular motors Structure and function of cilia and flagella 3 Power plan ENDOMEMBRANE SYSTEM HEADQUATER ER Nucleus Golgi 01 04 Endosome DIGESTION CENTER 02 03 POWER PLAN Lysosome Mitochondria Peroxisome Chloroplast Vacuole 4 2  10/9/24 MITOCHONDRIA “Power plan” of the cell. - Fatty acid oxidation (oxidative phosphorylation) - Krebs cycle (ATP synthesis) - Mitochondrial protein synthesis 2 membranes: - Outer membrane: perforated by porins, allow metabolite trafficking, but not most proteins. - Inner membrane: cristae housing electron transport chain (ETC). Have bacterial-type chromosomes (no introns) encoding tRNAs, rRNA, some components of ETC. mtDNA 103–104 mitochondria in mammalian cells pH ~ 8 Inner membrane Outer membrane 5 MITOCHONDRIA https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.623973/full 6 3  10/9/24 MITOCHONDRIAL ATP SYNTHESIS (2) pump H+ ions into intermembrane space as they transfer the electrons (3) H+ gradient powers ATP synthesis (4) ATP synthase rotary pump uses the energy generated by movement of H+ ions down their electrochemical gradient to turn the rotary subunits and synthesize ATP (1) transfers H from NADH and FADH2 to O2 7 https://www.youtube.com/watch?v=rdF3mnyS1p0&t=15s 8 4  10/9/24 MITOCHONDRIAL BIOGENESIS mitochondria divide and fuse Pollard et al., Cell Biology 3rd. 2017 9 MITOCHONDRIAL BIOGENESIS membrane contact point Translocon Lipid transfer protein ER 10 5  10/9/24 Heteroplasmy 11 Mitochondrion – related diseases 12 6  10/9/24 Three-Parent Baby Leigh Syndrome - Born in April 2016 MRT: mitochondrial replacement therapy https://www.thebridgeclinic.com/blog/three-parent-ivf-the-facts-the-benefits-the-concerns- 13 QUESTIONS Which cell type has: - no mitochondria - the highest number of mitochondria Highest number of mitochondria no mitochondrion red blood cells heart muscle cells- human oocyte- 5K mitochondria 100K-600K mitochondria Ross and Pawlina. Histology-A text and Atlas with correlated cell and molecular biology. 2016 14 7  10/9/24 Digestion center ENDOMEMBRANE SYSTEM HEADQUATER ER Nucleus Golgi 01 04 Endosome DIGESTION CENTER 02 03 POWER PLAN Lysosome Mitochondria Peroxisome Chloroplast Vacuole 15 Lysosome Ø 50 – 1,000 lysosomes/cell Ø pH ~ 4.8 Ø contains ~ 50 digestive enzymes (produced by RER) Ø digest most complex cell components: protein, glycogen, sphingolipids, proteoglycans, etc. What keeps a lysosome from digesting the entire cell? Lysosome pH: 4.8: for optimal lysosomal enzyme function Cytoplasm pH: neutral à inhibit lysosomal enzymes Cell injured by extreme cold, heat, or another physical stress à initiate cell death by bursting all lysosomes at once Hoefnagels. Biology: Concepts and Investigation. 2015 16 8  10/9/24 QUESTIONS Which cell type has: - no lysosome - the highest number of lysosomes no lysosome highest number of lysosomes red blood cells White blood cells to engulf and dispose of debris and bacteria Hoefnagels. Biology: Concepts and Investigation. 2015 17 Lysosome synthesis Lysosomal enzymes synthesized in rough ER, transported to Golgi for processing. Mannose-6-phosphate signal added to carbohydrate chains targeting the enzymes for a lysosomal receptor. Lysosome vesicles bud off from Golgi. Fuse with existing lysosomes or with other membrane-bound vesicles containing waste products to be digested. M-6-P: Mannose-6-phosphate Ross and Pawlina. Histology-A text and Atlas with correlated cell and molecular biology. 2016 18 9  10/9/24 Lysosome function uptake and digestion phagocyte Ø dismantle and recycle food particles, captured bacteria, worn-out organelles, misfolded protein, and debris Ø break down the large organic molecules into smaller subunits by hydrolysis, releasing them into the cytoplasm for the cell to use Ø Liver cells require many lysosomes to process break down bacteria and the debris from dead cells cholesterol. Widmaier. Vander’s Human Physiology. 2018 19 Autophagy Ø engulfment of large regions of cytoplasm Ø breakdown of cytoplasmic constituents within lysosomes Ø defense of single-celled organisms against starvation Ø Cargo may include glycogen granules, ribosomes, & organelles such as mitochondria and peroxisomes Pollard et al., Cell Biology 3rd. 2017 20 10  10/9/24 LYSOSOMAL DISORDERS Kidney cells in Deficiencies of lysosomal enzymes cause many Fabry Disease rare, genetic disorders: Sphingolipids – Fabry disease, Gaucher disease, Tay-Sachs disease, Krabbe disease Glycogen – Pompe disease Proteoglycans – Hurler syndrome, Hunter syndrome, Saniflippo syndrome. Glycosphingolipid- containing Defects in the mannose-6-phosphate transport lysosomes system leads to multiple enzyme deficiencies and causes Mucolipidosis II. The substances that cannot be degraded because of the enzyme deficiency accumulate in lysosomes in the cells and damage the cells. © 2011 Wikimedia Commons, Creative Commons License, User: Kuebi 21 QUESTIONS A human nerve cell that has an abnormal Imagine that you found a cell that releases many shape most likely has a defective proteins into the bloodstream. a. cell wall. What organelles might be especially active in this cell? b. cytoskeleton. What would each of these organelles be doing? c. nucleus. d. ribosome. Which of the following organelles are associated with the job of cellular digestion? a. Lysosomes and peroxisomes b. Golgi apparatus and vesicles c. Nucleus and nucleolus d. Smooth and rough endoplasmic reticulum 22 11  10/9/24 PROTEASOME/UBIQUITIN SYSTEM Proteins have defined half-lives and are degraded after they reach that limit. Ubiquitin © 2008 Wikimedia Some long-lived and membrane proteins are Commons, Creative Commons License, degraded in the lysosomes. User: Rogerdodd Others are degraded in proteasomes. Proteins to be degraded in the proteasome are tagged with ubiquitin. Ubiquitin is an abundant 76 amino acid protein. The C-terminal carboxyl group of ubiquitin is attached to a lysine side chain in the protein. Several ubiquitin molecules can be attached to each other in a chain. © 2020 OpenStax, Creative Commons License, Access for free at https://openstax.org/books/biology-2e/pages/1-introduction. 23 Peroxisome Ø All eukaryotic cells contain peroxisomes that surrounded by a single membrane. Ø Equipped with ~ 100 proteins Ø 50 enzymes identified, imported from cytoplasm Ø pH ~ 6.9 – 7.1 Oxidize 25% of the ethanol alcohol humans drink Hoefnagels. Biology: Concepts and Investigation. 2015 25 12  10/9/24 Peroxisome functions Ø Oxidize toxic substances- H2O2 oxidizes toxic chemicals, into less toxic compounds to be eliminated from the body. Ø Break fatty acids- into smaller molecules to send to cytosol to participate in anabolic reactions OR mitochondria to be oxidized to produce ATP Ø Synthesize plasmalogen phospholipids- critical plasma membrane components of specific cells in nervous system https://step1.medbullets.com/biochemistry/102081/peroxisome 26 Peroxisome synthesis possibility evolved as a specialization of the ER Hettema and Gould. Nature. 2017 27 13  10/9/24 Peroxisome – related diseases Zellweger spectrum disorders (ZSDs) § Phenotype: severe neuronal abnormalities, developmental delay and early death - Impaired peroxisome: normal peroxisomal membrane § Causes: proteins (PMPs), but lack enzymes - Lack peroxisomes: mutations in PEX3, PEX16 or PEX19, required for insertion of PMPs into peroxisome membrane § Treatment: gene therapy? drugs to increase the expression of peroxisomal genes https://www.healtheuropa.eu/zellweger-spectrum-disorders/88667/ 28 Inside the cell is mostly water. The cell membrane is fluidic in nature. Why does the cell not collapse? 29 14  10/9/24 Cytoskeleton 2014, Public Domain, Wikimedia Commons, Author: OgreBot 30 CYTOSKELETON COMPONENTS The cytoskeleton is the interior scaffolding and structural elements of the cell. Type of Size (D) Functions Protein Cytoskeleton; associates Microfilaments 7 nm Actin with myosin for muscle contraction Keratin, Intermediate Cytoskeleton, hair & nails, 10 nm neurofilament filaments protective barrier of skin protein Movement of cilia, flagella, & chromosomes; Microtubules 25 nm Tubulin intracellular transport of organelles; cytoskeleton © 2013 OpenStax, Creative Commons License.; 31 15  10/9/24 CYTOSKELETON FUNCTION Cell shape: provides mechanical strength and plays an important role in determining the shape of the cell Internal organization: stabilize the positions of organelles Intracellular transport: transport materials into the cell and within the cytoplasm by serving as an intracellular “railroad track” Assembly of cells into tissues: linking cells to one another and to supporting material outside the cells Movement: helps cells move. Makes up cilia and flagella; provides the structure and power to allow cells to change shape. Silverthorn et al. 2019. Human physiology: an integrated approach. 8th. Pearson 32 https://www.youtube.com/watch?v=tO-W8mvBa78 33 16  10/9/24 ACTIN FILAMENTS (MICROFILAMENTS) Actin filaments: form a structural network in cells and support cellular movements. Microvilli in intestinal cells are reinforced by actin filaments. Polymerization and depolymerization of actin filaments at the cell membrane allows phagocytosis Actin bind ATP, hydrolyze it to ADP when polymerize Actin filaments grow and shrink by adding or losing monomers from the ends. actin-binding proteins: participates in polymerization, depolymerization, crosslinking, capping and cutting of actin filaments. network of actin filaments: largely responsible for the viscoelastic properties of cytoplasm. 2008, Public Domain, WikiMedia Commons, Author: Mikael Häggström 34 ACTIN FILAMENTS (MICROFILAMENTS) diapedesis 35 17  10/9/24 https://www.youtube.com/watch?v=8TZgf1zaVgU 36 QUESTIONS Both the actin and myosin filaments of muscle are made up of subunits held together by weak noncovalent bonds, how is it possible for a human being to lift heavy objects? Although the subunits are indeed held together by noncovalent bonds that are individually weak, there are a very large number of them, distributed among a very large number of filaments. As a result, the stress a human being exerts by lifting a heavy object is dispersed over so many subunits that their interaction strength is not exceeded. 37 18  10/9/24 INTERMEDIATE FILAMENTS Type Name Functions Cell types Strong, flexible fibers that support cells. Structural integrity, Form a network between the plasma I & II Keratin mechanical resistance, - Epithelial cells membrane and nucleus. adhesion, motility… Made of a variety of proteins. - Vimentin - structure support, - many cells III motility, focal adhesion Provide mechanical resistance to stretch and - Desmin - contraction - muscle, cadiomyocyte deformation of cells. Structural support in IV Neurofilaments - neurons neuronal axons Structure support, V Nuclear lamins chromatin organization, - every cell types gene regulation Self-renewal, VI Nestin proliferation, survival, - stem cells migration… © 2019 SMART-Servier Medical Art, Creative Commons License. 38 INTERMEDIATE FILAMENTS Desmosomes: connect cell membranes at cell-cell junctions. Hemidesmosomes: connect cells into the extracellular matrix. Keratin IF network https://www.intechopen.com/chapters/53691 39 19  10/9/24 40 https://www.jci.org/articles/view/140615/pdf 41 20  10/9/24 QUESTION Which of the following types of cells would you expect to contain a high density of intermediate filaments in their cytoplasm? Explain your answers. 1. Amoeba proteus (a free-living amoeba) Cells that migrate rapidly from one place to another, such as 2. Skin epithelial cell amoebae (1) and sperm cells (5), do not in general need intermediate filaments in their cytoplasm, since they do not 3. Smooth muscle cell in the digestive tract develop or sustain large tensile forces. 4. Escherichia coli Plant cells (6) are pushed and pulled by the forces of wind and 5. Sperm cell water, but they resist these forces by means of their rigid cell walls rather than by their cytoskeleton. 6. Plant cell Escherichia coli (4) do not have filaments Epithelial cells (2), smooth muscle cells (3), are all rich in cytoplasmic intermediate filaments, which prevent them from rupturing as they are stretched and compressed by the movements of their surrounding tissues. 42 MICROTUBULES Microtubules: stiff cylinders made of 𝛼 and 𝛽 tubulin monomers. Provide structural support for cells. Provide tracks for movement of metabolites and cell components. Form the mitotic spindle. Form some of the structural elements of cilia and flagella. Microtubules grow from a centrosome. Motor proteins, dynein and kinesins bind to microtubules to drive movements along the tubules, or the beating of cilia and flagella. © 2020 Wikimedia Commons, Creative Commons License, User: PKS615 43 21  10/9/24 CENTROSOMES Centrosomes are the most common microtubule organizing centers (MTOCs). 2 centrioles arranged at right angles at center. Microtubules grow radially from centrioles. Centrioles: a bundle of 9 doublets or triplets of microtubules. Centrosome Microtubules radiating from the centrosome help organize organelles in the cell. Centrioles form the basal bodies that anchor cilia and flagella. https://www.visiblebody.com/blog/mitosis-and-meiosis-whats-the-difference © 2013 Wikimedia Commons, Creative Commons License, User: Kelvin13 44 MICROTUBULE MOTOR PROTEINS Kinesin & dynein bind to microtubules and move other molecules (cargo) along the tubules. Cargo: vesicles, organelles, chromosomes or molecules. Motor proteins: heads bind to tubulin, tails bind the cargo. They hydrolyze ATP to “walk” along the microtubule. tail head 45 22  10/9/24 CILIA AND FLAGELLA Cilia and flagella: movable extensions of the inner cell skeletal architecture (cytoskeleton). Made up of microtubules, dynein and associated proteins. The only cell with a flagellum in an adult is the sperm cell. Motile cilia are expressed to: - move mucus in the respiratory tract upward toward the mouth. - move the ovum through the oviducts. - circulate cerebrospinal fluid in the lining of the https://epithelium3d.com/trachea ventricles of the brain. Sperm flagellum © 2019 SMART-Servier Medical Art, Creative Commons License. 46 CILIA AND FLAGELLA Cilia and flagella: axoneme with 9 microtubule doublets surrounding a pair of central microtubules (9+2). The outer doublets are connected to arms made of dynein. 200 accessory proteins attach to the 9+2 architecture to hold the doublets in place and anchor them to the central doublet with spokes. Cilia and flagella grow from a basal body. 9 doublets grow from the 9 triplets in the centriole. ATP hydrolysis powers the dynein proteins to make the outer doublets slide in relation to each other, bending the axoneme and causing motion. 2007, Public Domain, Wikimedia Commons, Author: LadyofHats 47 23  10/9/24 https://www.youtube.com/watch?v=9nZYlyFGm50 48 QUESTIONS One result of cigarette smoking is paralysis of the cilia that line the respiratory passageways. What function do these cilia serve? Why is it harmful when they no longer beat? What health problems would you expect to arise? How does this explain the hacking cough common among smokers? Cilia sweep mucus and particles, chemicals from the tobacco use up and out of the airways. When they fail, inhaled pathogens are more likely to reach the lungs and chemicals from the tobacco use stay. This results in infections, inflammation, or cancer. The smoker’s cough removes the mucus/chemicals that would normally be swept away by the cilia. 49 24  10/9/24 Who is Who? 9 1 1. Nucleolus 8 Cytoplasm 2. ER 10 3. Ribosome 4. Golgi complex 2 5. Mitochondrion 7 6. Smooth ER 7. Peroxisome 3 8. Microvilli 6 5 9. Flagellum 4 10. Centrioles 50 LECTURE SUMMARY Mitochondria - Mitochondrial ATP synthesis - Mitochondrial biogenesis Peroxisomes Lysosomes Proteasomes/ubiquitin Cytoskeleton - Microtubules - Actin filaments - Intermediate filaments - Molecular motors Cilia, Flagella Silverthorn et al. 2019. Human physiology: an integrated approach. 8th. Pearson 51 25  10/9/24 End: Cell Structure 2 © 2012 Wikimedia Commons, Creative Commons License, User: Kelvin13 52 LYSOSOMAL DISORDERS Lysosomal enzymes are glycosylated and modified in a characteristic way. Most importantly, when they arrive in the Golgi apparatus, specific mannose residues in their oligosaccharide chains are phosphorylated. This phosphorylation is the critical event that removes them from the secretion pathway and directs them to lysosomes. Genetic defects affecting this phosphorylation produce I-cell disease in which lysosomal enzymes are released into the extracellular space, and inclusion bodies accumulate in the cell, compromising its function. Major symptoms of I-cell disease - Coarse facial features, gingival hyperplasia, macroglossia - Craniofacial abnormalities, joint immobility, club-foot, claw-hand, scoliosis - Psychomotor retardation, growth retardation - Cardiorespiratory failure, death in first decade 60 26