Lysosomes, Smooth Endoplasmic Reticulum, Mitochondria, and Inclusions

5. Lysosomes, Smooth Endoplasmic Reticulum, Mitochondria, and Inclusions Objective Lysosomal ultrastructure and function/dysfunction along with continued discussion on protein sorting and protein targeting Smooth endoplasmic reticulum ultrastructure and function in typical cells and those specialized to secrete steroids Mitochondrial ultrastructure, function, origin, and incorporation of cytoplasmic proteins Inclusions Ribosomes translate mRNA in the production of protein. SER Reactions Cytosolic proteins • Scaler reactions a+b=c • Vectorial reactions a+b = c membranes RER proteins • Cytosol is the watery part of the cytoplasm that is not held by any of the organelles in the cell. On the other hand and other than the nucleus, cytoplasm is the part of the cell which is contained within the entire cell membrane. • Cytoplasm is cytosol plus organelles = every thing between the cell membrane and the nuclear envelope Cytosolic proteins RER proteins Scaler reactions Vectorial reactions Lysosome Ultrastructure Secondary lysosomes Usually varied in the staining intensity within each Lysosome Enzymes present phosphatases, proteases, nucleases, lipid degrading enzymes Lysosome Method of detection - localization of enzymes as primary lysosomes look like secretory granules Histochemical reaction using the local enzyme plus substrate to produce black precipitate Localization of lysosomal enzymes Lysosome Negative charges on inner leaflet of lysosomal membrane - protect from enzymes degradation Post-translational = Cisternal and post-cisternal phases of secretion ? Induced secretion Mannose-6-Phosphate lysosome via receptors Hence, phosphorylation occurs in the Golgi apparatus as well as the addition of sugar, fatty acids, and sulfate groups to proteins = signal for sorting enzyme to Function / actions of lysosomes Programmed cell death – Remodeling as in an embryo or tadpole (frog) Function / actions of lysosomes Housekeeping function – Remove worn organelles (autophagy) Function / actions of lysosomes Unprogrammed cell death Damage/death to cardiac cells in ischemia associated with myocardial infarctions PRE-STENT POST-STENT In summary: Membranes allow cells a high degree of chemical heterogeneity How does membranes and chemical heterogeneity facilitate lysosomal functions? Surfaces and interfaces - sites important for physiological processes Enzymes - catalyze chemical transformations Internal partition of cytoplasm - enzymes, substrates, products Efficiency of complex chemical reaction amplified area Gradients - by permeability and rate of active transport Regulate cell’s activity Hold reserve a large repertoire of unexpressed biochemical reactions Function / actions of lysosomes Heterophagy Ingest and digest things outside the cell Heterophagy LYSOSOME LATENCY CHARACTERISTIC LEAD TO DISCOVERY OF LYSOSOMES RESULTS FROM ENZYME BEING LOCATED WITHIN MEMBRANES RESIDUAL BODY REMAIN AFTER DIGESTION HAS STOPPED = LIPOFUSCIN Lysosome Lysosome storage disease ( I-cell disease or inclusion disease) = No mannose-6-phosphate (no signal for sorting enzyme to lysosome) • No enzymes in lysosomes I-cell individuals • Undigested inclusions accumulate inside the cell Enzymes are constitutively released Lysosomes (summary) • Single membrane • Rich hydrolytic enzymes (50 enzymes) • Enzymes safely contained by membrane • Pathological conditions • Primary lysosomes produced by RER and Golgi • Mannose-6-phosphate on protein signals for transport of enzymes into lysosomes Functions (summary) • Cell digestion - embryonic development • Defense against microbial invasion • Intracellular digestion of cellular material – Residual bodies, exocytosis • Autophagic vacuole • Primary lysosome • Secondary lysosome (enzymes of primary + substrate) Smooth endoplasmic reticulum • Smooth membrane Lipid droplets have no membrane around them = inclusion/nutrient lipid Smooth endoplasmic reticulum • Origin of SER and its enzymes is RER EM 4c Cut Perpendicular to height of the cell EM 4c Membrane and receptors RER, Golgi, and secretion Smooth endoplasmic reticulum • Function: – Synthesis & transport of lipids in the intestinal absorptive cell Central lacteal Central lacteal Smooth endoplasmic reticulum • Function: Detoxification in liver Toxicology What is toxicology? The study of the effects of poisons. Poisonous substances are produced by plants, animals, or bacteria. Phytotoxins Zootoxins Bacteriotoxins Toxicant - the specific poisonous chemical. Xenobiotic - man-made substance and/or produced by but not normally found in the body. Introduction to Xenobiotics *Recall: Foreign chemicals that are synthesized within the body are termed xenobiotics (Gr.Xenos meaning “strange”)* • Xenobiotics may be naturally occurring chemicals synthesized by plants, microorganisms, or animals (including humans). • Xenobiotics may also be synthetic chemicals synthesized by humans. Poisons are xenobiotics, but not all xenobiotics are poisonous. Xenobiotics at Work TOXICOKINETICS Xenobiotic Excretion General Scheme of Xenobiotic Metabolism Lipophilic (parent compound) Metabolism Phase I (oxidative) Bioactivation Detoxification Hydrophilic (metabolite) 1) Decrease biological activity 2) Increase excretability Metabolites polarity functionality Phase II (synthetic) Detoxification Metabolites size ionization water solubility Increase excretability Smooth endoplasmic reticulum • Function: – Steroid synthesis Smooth endoplasmic reticulum • Function: – Ca++ Regulation in muscle cells Smooth endoplasmic reticulum The sarcoplasmic reticulum is smooth endoplasmic reticulum SER - structure and function (summary) No ribosomes (smooth surface) – No ribophorin receptors to bind them Synthesis of triglycerides, cholesterol, and steroids Has enzymes for conjugation, oxidation, and methylation Metabolizes and detoxifies drugs Lipid droplet Sequester and release Ca++ – Muscle contraction (sarcoplasmic reticulum) Mitochondria – convert sun energy stored in food (plant and animal) into a usable source (ATP high-energy bond) for biosynthesis & movement Mitochondria - energy for biosynthesis & movement • Size = 0.3 um X 4 um • Double membrane – Smooth contoured outer membrane – Inner membrane forms cristae (number related to energy requirement) Mitochondria - energy for biosynthesis & movement Two compartments Larger intercristal space Intracristal space • Inner membrane cytochrome oxidase and other enzymes • Subunits projecting into space – enzymes for oxidative phosphorylation of ADP and hydrolysis of ATP Mitochondria Mitochondria - energy for biosynthesis & movement Mitochondria are found where energy is needed in cells Mitochondria - energy for biosynthesis & movement Mitochondria are found where energy is needed as in these intestinal absorptive cells. Mitochondria - energy for biosynthesis & movement Mitochondria are found where energy is needed as in these cardiac cells Mitochondria Mitochondria - energy for biosynthesis & movement Mitochondria are found where energy is needed as in these cardiac cells Mitochondria Functions of mitochondria Make ATP, Kreb’s cycle enzymes Cellular respiration occurs in mitochondria. Mitochondria Cellular respiration is the process by which organic compounds (preferably glucose) are broken apart, releasing energy that is used to produce ATP molecules. ATP is a high energy nucleotide which acts as an instant source of energy within the cell (both plants and animals). http://antranik.org/intro-to-cellular-respiration-the-production-of-atp/ Cellular respiration occurs in mitochondria. mitochondria C6H12O6 + 6 O2 —– enzymes & coenzymes ——> 6 CO2 + 6 H2O + Release of Energy (≤38 ATP) + Heat In order to make ATP, you need food (sugar) and oxygen. You need oxygen to unlock the energy that’s in the food. Cellular respiration also explains why we are breathing oxygen in, why we exhale carbon dioxide out as well as why we are warm blooded. From where does the earth’s oxygen come? • Plants • In the process of photosynthesis, phytoplankton (tiny ocean plants) release oxygen into the water. Over half of the world's oxygen is produced via phytoplankton photosynthesis. Oxygen is also produced via photosynthesis on land by trees, shrubs, grasses, and other plants. Transport in/within mitochondria Transport in/within mitochondria How about transport of O2, CO2, and water? C6H12O6 + 6O2 —– enzymes & coenzymes ——> 6CO2 + 6H2O + Release of Energy (≤38 ATP) + Heat Membrane Transport in/within mitochondria. Mitochondria - double membrane How about transport of enzymes? Cytosolic proteins incorporation Mitochondria - double membrane Cytosolic proteins Cytosolic proteins incorporation Proteins in inner membrane of mitochondria • Transport • Respiration – electron transport chain • ATP synthesis • Krebs cycle - generate •proton (pH) gradient Functions of mitochondria Store Ca++ Mitochondria – Double membrane Varied shapes of cristae Mitochondria - double membrane • Ultrastructure - outer membrane, cristae, and matrix. However, cristae may be lamellar or tubular shapes Protein-secreting cell Steroid-secreting cell Functions of mitochondria Cholesterol - side chain cleavage in steroid synthesis Mitochondria - double membrane Origin Chloroplasts, like mitochondria, have double membranes, their own DNA, and enjoy a symbiotic relationship inside the cell. Both chloroplasts and mitochondria are believed to have been engulfed by ancient eukaryotic cells to become functional organelles in current eukaryotic cells. Symbiotic relationship of the clownfish and sea anemone. From where do mitochondria come? • Mitochondria duplicate by division • Mitochondria come from other mitochondria All your mitochondria came from your mother. Thank your Mom for all the mitochondria! Mitochondria - double membrane • Origin – Use nuclear and mitochondria DNA and mitochondrial ribosomes for biogenesis Mitochondria double membrane Use nuclear and mitochondria DNA and mitochondrial ribosomes for biogenesis Inclusions - expendables inside cells Nutrients – Glycogen – Lipid Inclusions - expendables inside cells Secretory granules Pancreas Intestine Paneth cells Goblet cells Inclusions - expendables inside cells Pigments – Melanin granules Inclusions - expendables inside cells Pigments – Lipofuscin Inclusions - expendables inside cells Pigments – Lipofuscin