2. Department of Physiology IIMC Cell Organelles 01 Dr.Abubakkar Siddique PGT, IIMC

3. Learning Objectives At the end of this presentation the PGTs should be able to answer the following questions Describe the functions of Endoplasmic Reticulum Describe the structure of Golgi Apparatus Enlist functions of Lysosomes & Peroxisomes Describe the formation of Secretory vesicles Elaborate the process of Endocytosis

4. Cytoplasmic organelles

5. Endoplasmic Reticulum

6. Endoplasmic reticulum (ER)  Literally means “network within the cytoplasm”  Is an extensive system of interconnected tubes and parallel lipid bilayer membranes enclosing fluid filled cavities, or cisterns  The lumen of endoplasmic reticulum contains a fluid medium called endoplasmic matrix  Coiling and twisting through the cytosol, the ER is continuous with the outer nuclear membrane and accounts for about half of the cell’s membranes

8. Types of Endoplasmic Reticulum  On the basis of the presence or absence of ribosomes on outer membranous surface of ER,when viewed with an electron microscope, it is divided into two types: 1.Rough Endoplasmic Reticulum 2.Smooth Endoplasmic Reticulum

10. Rough Endoplasmic Reticulum  The external surface of the rough ER is studded with ribosomes, hence the name “rough”  Proteins assembled on these ribosomes thread their way into the fluid-filled interior of the ER cisterns  When complete, the newly made proteins are enclosed in vesicles for their journey to the Golgi apparatus where they undergo further processing

11. Functions of Rough ER 1. Synthesis of proteins o Its ribosomes manufacture all proteins secreted from cells o For this reason, the rough ER is well developed in most secretory cells, antibody-producing plasma cells, and liver cells o It is also the cell’s “membrane factory” where integral proteins and phospholipids that form part of all cellular membranes are manufactured 2.Degradation of worn-out organelles via formation of “the autophagosome”

15. Smooth Endoplasmic Reticulum  ER that lacks ribosomes is called Smooth ER  Is continuous with the rough ER and consists of tubules arranged in a looping network  Its enzymes (all integral proteins forming part of its membranes) play no role in protein synthesis  It synthesizes macromolecules other than protein

16. Smooth ER

17. Functions of Smooth ER 1.Metabolize lipids, synthesize cholesterol, and synthesize the lipid components of lipoproteins (in liver cells) 2.Synthesize steroid-based hormones such as sex hormones (testosterone-synthesizing cells of the testes) 3.Absorb, synthesize, and transport fats (in intestinal cells)

18. Functions of Smooth ER 5.Detoxify drugs, certain pesticides, and cancer- causing chemicals (in liver and kidneys) 6.Break down stored glycogen to form free glucose (in liver cells especially) 7.Skeletal and cardiac muscle cells have an elaborate smooth ER called the sarcoplasmic reticulum that plays an important role in storing and releasing calcium ions during muscle contraction

20. Golgi Apparatus

21. Golgi apparatus  A Golgi apparatus is a stack of half a dozen or so flattened, membranous sacs called cisternae  This organelle refines, packages, and delivers proteins synthesized on the rough ER

24. Golgi apparatus  As the glycoproteins pass from layer to layer through the Golgi stacks, they are modified chemically  When the altered glycoproteins reach the outermost layer, they are packaged in bits of Golgi apparatus membrane that bud off and form transport vesicles  Such a vesicle may then move to the cell membrane, where it fuses and releases its contents to the outside of the cell as a secretion

28. Cytoplasmic Vesicles

29. Types Membrane-bound cytoplasmic vesicles are of three kinds:  Secretory  Storage  Endocytotic

31.  Secretory vesicles contain proteins that will be released from the cell. They migrate to the plasma membrane and release their contents outside the cell by exocytosis  Storage vesicles, however, never leave the cytoplasm e.g. Lysosomes & Peroxisomes  Endo-cytotic vesicles These structures enclose bacteria and raw materials from the extracellular environment. They bring them into the cell by endocytosis

33. Lysosomes  Lysosomes are the “garbage disposals” of the cell, where enzymes dismantle debris  Lysosomes can be difficult to identify because their shapes vary so greatly, but they often appear as tiny, membranous sacs  These sacs contain powerful enzymes that break down proteins, carbohydrates, and nucleic acids, including foreign particles

35. Lysosomes  Certain white blood cells, for example, engulf infecting bacteria, which lysosomal enzymes then digest  Lysosomes fuse with endocytotic vesicles within the cell, digesting bacteria and other large objects  Lysosomes also perform certain housekeeping tasks, such as dissolving and removing damaged mitochondria and other cellular debris

37. Mechanism of lysosomal function  Heterophagy:  Digestion of extracellular materials engulfed by the cell via endocytosis  Autophagy:  Digestion of intracellular materials such as worn-out cytoplasmic organelles

38. Functions of lysosomes  Degradation of macromolecules  Degradation of worn-out organelles  Removal of excess secretory products in the cells  Secretory function – secretory lysosomes

39. Degradation of Macromolecules  Macromolecules are engulfed by the cell by means of endocytosis  Macromolecules such as bacteria, engulfed by the cell via phagocytosis are called phagosomes  Macromolecules taken inside via pinocytosis or receptor-mediated endocytosis are called endosomes  The primary lysosome fuses with the phagosome or endosome to form the secondary lysosome

40. Degradation of worn-out organelles  The rough endoplasmic reticulum wraps itself around the worn-out organelles like mitochondria and form the vacuoles called autophagosomes  One primary lysosome fuses with one autophagosome to form the secondary lysosome  The enzymes in the secondary lysosome are activated  These enzymes digest the contents of autophagosome

41. Lysosomes  Lysosomal membrane is able to withstand being digested because this organelle sequesters enzymes that can function only under very acidic conditions (100 times the cytoplasm), preventing them from destroying the cellular contents around them

43. Lysosomes  Digestive task is complete they become “residual bodies,” analogous to small bags of compacted waste  Residual bodies can be stored in the cell, but usually their contents are eliminated from the cell by exocytosis

44. Lysosomal Diseases  An abnormality in just one type of lysosomal enzyme can be devastating to health  When a lysosomal enzyme is congenitally absent, the lysosomes become engorged with the material the enzyme normally degrades. This eventually leads to one of the lysosomal diseases  There are over 50 such diseases currently recognized

46. Peroxisomes  Peroxisomes are 0.5 μm in diameter, are surrounded by a membrane, and contain enzymes that can either produce H2O2 (oxidases) or break it down (catalases)  Proteins are directed to the peroxisome by a unique signal sequence with the help of protein chaperones and peroxins

48.  Although present in all human cells, peroxisomes are most abundant in cells of the liver and kidneys  Peroxisomes contain enzymes, called peroxidases, that catalyze metabolic reactions that release hydrogen peroxide, which is toxic to cells  Peroxisomes also contain an enzyme called catalase, which decomposes hydrogen peroxide to oxygen and water

49.  The outer membrane of a peroxisome contains some forty types of enzymes, which catalyze a variety of biochemical reactions, including  synthesis of bile acids, used in fat digestion  breakdown of lipids called very long chain fatty acids  degradation of rare bio-chemicals  detoxification of alcohol

50.  Peroxisomal disorders disrupt the normal processing of lipids and can severely disrupt neural function by altering the structure of nerve cell membranes

51. SECRETORY VESICLES  Secretory vesicles are the organelles with limiting membrane and contain the secretory substances  These vesicles are formed in the endoplasmic reticulum and are processed and packed in Golgi apparatus  Secretory vesicles are present throughout the cytoplasm  When necessary, these vesicles are ruptured and secretory substances are released into the cytoplasm

53. Endocytosis

54.  Endocytosis, the reverse of exocytosis, refers to the internalization of extracellular material within a cell  Endocytosis can be accomplished in three ways— pinocytosis, receptor-mediated endocytosis, and phagocytosis—depending on the contents of the internalized material

56. PINOCYTOSIS  In pinocytosis (“cell drinking”), a droplet of ECF is taken up non-selectively  First, the plasma membrane dips inward, forming a pouch that contains a small bit of ECF.  The plasma membrane then seals at the surface of the pouch, trapping the contents in a small, intracellular endosome  Dynamin, the protein responsible for pinching off an endocytic vesicle, forms rings that wrap around and “wring the neck” of the pouch, severing the vesicle from the surface membrane

58. RECEPTOR-MEDIATED ENDOCYTOSIS  Unlike pinocytosis, which involves the nonselective uptake of the surrounding fluid, receptor-mediated endocytosis is a highly selective process that enables cells to import specific large molecules that it needs from its environment  Receptor ­mediated endocytosis is triggered by the binding of a specific target molecule such as a protein to a surface membrane receptor specific for that molecule

60.  This binding causes the plasma membrane at that site to pocket inward and then seal at the surface, trapping the bound molecule inside the cell.  The pouch is formed by the linkage of clathrin molecules, which are membrane deforming coat proteins on the inner surface of the plasma membrane. The resulting pouch is known as a coated pit

61.  Cholesterol complexes, vitamin B12, the hormone insulin, and iron are examples of substances selectively taken into cells by receptor­ mediated endocytosis  Flu viruses and HIV virus, gain entry to cells via receptor ­mediated endocytosis

62. PHAGOCYTOSIS  During phagocytosis (“cell eating”), large multi- molecular particles are internalized.  Only a few specialized cells are capable of phagocytosis  When a white blood cell encounters a large particle, such as a bacterium or tissue debris, it extends surface projections known as pseudopods (“false feet”) that surround or engulf the particle and trap it within an internalized vesicle

64.  A lysosome fuses with the membrane of the phagocytic vesicle and releases its hydrolytic enzymes into the vesicle, where they safely attack the bacterium or other trapped material without damaging the remainder of the cell  The enzymes largely break down the engulfed material into raw ingredients, such as amino acids, glucose, and fatty acids, that the cell can use

67. References Hall, John E. (John Edward), (2016). Guyton and Hall textbook of medical physiology. Philadelphia, Philadelphia: Elsevier, Inc. Lauralee Sherwood, (2013). Human physiology: from cells to systems. Belmont, California: Brooks/Cole, Cengage Learning. Kim E. Barrett, (2016). Ganong’s review of medical physiology. New York City, New York: McGraw-Hill Education. K. Sembulingam, (2016). Sembulingam’s Essentials of Medical Physiology. New Delhi, India: Jaypee Brothers Medical Publishers Ltd.

68. "Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning." Winston Churchill Thank You!