The Cell & Organelles PDF

The Cell & Organelles Dr. Hilal Eren Gözel Faculty of Medicine, Department of Medical Biology & Genetics I. Okan University Contact Info [email protected] 1st Floor – Office #129 Objectives The secrets of Cell...

The Cell & Organelles Dr. Hilal Eren Gözel Faculty of Medicine, Department of Medical Biology & Genetics I. Okan University Contact Info [email protected] 1st Floor – Office #129 Objectives The secrets of Cell Hidden jewels: Organelles Clinical Correlations  The Cell Cells are the basic structural and functional units of all multicellular organisms. Cells can be divided into two major compartments: the cytoplasm and the nucleus. In general, the cytoplasm is the part of the cell located outside the nucleus.  The Cell – Cytoplasmic Matrix (Cytosol) Cytoplas. matrix + organelles + inclusions = Cytoplasm The matrix consists of a variety of solutes, including inorganic ions (Na+, K+, Ca2+) and organic molecules such as intermediate metabolites, carbohydrates, lipids, proteins, and RNAs. (pH: 7.2) The cytoplasmic matrix is the site of physiologic processes that are fundamental to the cell’s existence (protein synthesis, breakdown of nutrients). Inclusions are not usually surrounded by a plasma membrane. They consist of such diverse materials as crystals, pigment granules, lipids, glycogen, and other stored waste products.  The Cell – Organelles An organelle is a specialized structures within a cell that perform a specific function. Like organs in the body!! Organelles are described as Membranous organelles with plasma membranes that separate the internal environment of the organelle from the cytoplasm, Nonmembranous organelles without plasma membranes.  The Cell – Organelles The Membraneous organelles: The Nonmembraneous organelles: Plasma (Cell) membrane Ribosome Endoplasmic reticulum Microtubules and filaments Centriole Golgi apparatus Mitochondria Lysosome Endosomes, peroxisomes, transport vesicles  The Cell – Nucleus The nucleus contains most of the cell’s genes and is usually the most conspicuous organelle - averaging about 5 μm in diameter. Components of Nucleus: Nuclear membrane Chromatin Nucleolus  The Cell – Nucleus The nuclear envelope encloses the nucleus, separating it from the cytoplasm. The nuclear membrane is a double membrane; each membrane consists of a lipid bilayer.  Nucleus The two membranes, each a lipid bilayer with associated proteins, are separated by a space of 20–40 nm. The envelope is perforated by pore structures that are about 100 nm in diameter.  Nucleus At the lip of each pore, the inner and outer membranes of the nuclear envelope are continuous. An intricate protein structure called a pore complex lines each pore and plays an important role in the cell by regulating the entry and exit of proteins and RNAs, as well as large complexes of macromolecules.  Nucleus The nuclear side of the envelope is lined by the nuclear lamina, a netlike array of protein filaments that maintains the shape of the nucleus by mechanically supporting the nuclear envelope.  Nucleus 1 µm Nucleolus Chromatin Nuclear envelope: Inner membrane Outer membrane Nuclear pore Pore complex Rough ER Surface of nuclear envelope Ribosome 1 µm 0.25 µm Close-up of nuclear envelope Pore complexes (TEM) Nuclear lamina (TEM)  Nucleus In the nucleus, DNA and proteins form genetic material called chromatin. Chromatin condenses to form discrete chromosomes. Some of the proteins help coil the DNA molecule of each chromosome, reducing its length and allowing it to fit into the nucleus (histon). A typical human cell has 46 chromosomes in its nucleus; the exceptions are the sex cells (eggs and sperm), which have only 23 chromosomes in humans. Nucleus  Nucleus In most cells, chromatin does not have a homogeneous appearance; rather, clumps of densely staining chromatin are embedded in a more lightly staining background. The densely staining material is highly condensed chromatin called heterochromatin, and the lightly staining material (where most transcribed genes are located) is a dispersed form called euchromatin. Nucleus Heterochromatin Euchromatin  Nucleolus The nucleolus (pl., nucleoli) is a small area within the nucleus that contains DNA in the form of transcriptionally active ribosomal RNA (rRNA) genes, RNA, and proteins. The nucleolus is the site of rRNA synthesis and contains regulatory cell-cycle proteins. It is the primary site of ribosomal production and assembly. Some cells contain more than one nucleolus.  Ribosome Ribosomes are particles made of ribosomal RNA and proteins. Ribosomes carry out protein synthesis in two locations: In the cytosol (free ribosomes) On the outside of the endoplasmic reticulum or the nuclear envelope (bound ribosomes) Bound and free ribosomes are structurally identical, and ribosomes can alternate between the two roles. Ribosome Fig. 6-11 Cytosol Endoplasmic reticulum (ER) Free ribosomes Bound ribosomes Large subunit Small 0.5 µm subunit TEM showing ER and ribosomes Diagram of a ribosome  Ribosome Most of the proteins made on free ribosomes function within the cytosol; examples are enzymes that catalyze the first steps of sugar breakdown (e.g. Hexokinase). Bound ribosomes generally make proteins that are destined for insertion into membranes, for packaging within certain organelles such as lysosomes, or for export from the cell (secretion). Cells that specialize in protein secretion—for instance, the cells of the pancreas that secrete digestive enzymes—frequently have a high proportion of bound ribosomes.  Clinical Correlation: Ribosome Ribosomopathies are diseases caused by alterations in the structure or function of ribosomal components. Clinical features of the ribosomopathies can include bone marrow failure, developmental abnormalities, and increased risk of cancer. However, ribosomal dysfunction can cause a wide range of signs and symptoms, and presentation and severity can differ dramatically even among patients with the same diagnosis.  Clinical Correlation: Ribosome Ref: Nakhoul, H., Ke, J., Zhou, X., Liao, W., Zeng, S. X., & Lu, H. (2014). Ribosomopathies: mechanisms of disease. Clinical Medicine Insights: Blood Disorders, 7, CMBD-S16952.  The Endoplasmic Reticulum The endoplasmic reticulum (ER) (The word endoplasmic means “within the cytoplasm,” and reticulum is Latin for “little net.”) consists of a network of membranous tubules and sacs called cisternae. The ER membrane is continuous with the nuclear envelope There are two distinct regions of ER: Smooth ER, which lacks ribosomes Rough ER, with ribosomes studding its surface The Endoplasmic Reticulum  Smooth ER Rough ER Nuclear envelope The Endoplasmic ER lumen Reticulum Cisternae Ribosomes Transitional ER Transport vesicle 200 nm Smooth ER Rough ER  The Rough Endoplasmic Reticulum The rough ER; Has bound ribosomes, which produce secretory proteins which are mostly glycoproteins (proteins covalently bonded to carbohydrates) Distributes transport vesicles, proteins surrounded by membranes Is a membrane factory for the cell (adds membrane proteins and phospholipids)  The Smooth Endoplasmic Reticulum The smooth ER; Synthesizes lipids (oils, phospholipids, and steroids), Metabolizes carbohydrates, Stores calcium (triggers muscle contraction), Detoxifies poison and drugs (adding hydroxyl groups to drug molecules, making them more soluble and easier to flush from the body).  The Smooth Endoplasmic Reticulum The sedative phenobarbital and other barbiturates are examples of drugs metabolized in this manner by smooth ER in liver cells. In fact, barbiturates, alcohol, and many other drugs induce the proliferation of smooth ER and its associated detoxification enzymes, thus increasing the rate of detoxification. This, in turn, increases tolerance to the drugs, meaning that higher doses are required to achieve a particular effect, such as sedation. Also, because some of the detoxification enzymes have relatively broad action, the proliferation of smooth ER in response to one drug can increase tolerance to other drugs as well. Barbiturate abuse, for example, can decrease the effectiveness of certain antibiotics and other useful drugs.  The Smooth Endoplasmic Reticulum Among the steroids produced by the smooth ER in animal cells are the sex hormones of vertebrates and the various steroid hormones (androgens, estrogens, and progestogens) secreted by the adrenal glands. The cells that synthesize and secrete these hormones—in the testes and ovaries, for example—are rich in smooth ER, a structural feature that fits the function of these cells.  The Golgi Apparatus The Golgi apparatus consists of flattened membranous sacs called cisternae. Functions of the Golgi apparatus: Modifies/stores/sends products of the ER Manufactures certain macromolecules Sorts and packages materials into transport vesicles Add molecular identification tags as address in mailing labels. The Golgi Apparatus cis face ( receiving side of Golgi 0.1 µm apparatus) Cisternae trans face ( shipping side of Golgi TEM of Golgi apparatus apparatus)  Lysosome Digestive compartment of cell. A lysosome is a membranous sac of hydrolytic enzymes that can digest macromolecules Lysosomal enzymes can hydrolyze proteins, fats, polysaccharides, and nucleic acids Lysosomal enzymes work best in the acidic environment found in lysosomes. If a lysosome breaks open or leaks its contents (enzymes) into the cell, does the cell be digested???  Nucleus 1 µm Some types of cell can engulf another cell by phagocytosis; this forms a food vacuole Lysosome Digestive A lysosome fuses with Lysosome enzymes the food vacuole and Plasma digests the molecules membrane Digestion Food vacuole (a) Phagocytosis Macrophages, a type of white blood cell that helps defend the body by engulfing and destroying bacteria and other invaders  Vesicle containing 1 µm two damaged organelles Mitochondrion Lysosomes also use enzymes fragment to recycle the cellʼs own Peroxisome fragment organelles and macromolecules, a process called autophagy Lysosome Peroxisome Mitochondrion Digestion Vesicle (b) Autophagy  Clinical Correlation: Lysosome Lysosomal Storage Diseases (LSDs) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. The accumulation of substrates in excess in various organs' cells due to the defective functioning of lysosomes causes dysfunction of those organs. Clinical Relation: Lysosome Metachromatic leukodystrophy Sphingolipidoses – Type of lipid Mucopolysaccharidoses Type of sugar  Mitochondrium Mitochondria change energy from one form to another! Mitochondria are the sites of cellular respiration, a metabolic process that generates ATP. Mitochondria; Have a double membrane Have proteins made by free ribosomes Contain their own DNA (mtDNA)  Mitochondrium Mitochondria have a smooth outer membrane and an inner membrane folded into cristae. The inner membrane creates two compartments: intermembrane space and mitochondrial matrix. Some metabolic steps of cellular respiration are catalyzed in the mitochondrial matrix. Cristae present a large surface area for enzymes that synthesize ATP. Mitochondrium Intermembrane space Outer membrane Free ribosomes in the mitochondrial matrix Inner membrane Cristae Matrix 0.1 µm  Mitochondrium Not just Energy!! Cytochrome c à Initiates apoptosis (programmed cell death!) Heat production! Thermogenin in brown adipose tissue. Ca2+ storage (secondary messenger) à coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells. Steroid synthesis Mature Erythrocytes do not have Mitochondria!!  Mitochondrium Endosymbiont theory Mitochondria and chloroplasts display similarities with bacteria. Theory states that an early ancestor of eukaryotic cells engulfed an oxygen-using nonphotosynthetic prokaryotic cell. Eventually, the engulfed cell formed a relationship with the host cell in which it was enclosed, becoming an endosymbiont (a cell living within another cell). Endosymbiont theory  Mitochondrium Endosymbiont theory – Evidences: The ancestral engulfed prokaryotes had two outer membranes, which became the double membranes of mitochondria and chloroplasts. Like prokaryotes, mitochondria and chloroplasts contain ribosomes, as well as circular DNA molecules attached to their inner membranes. The DNA in these organelles programs the synthesis of some of their own proteins, which are made on the ribosomes inside the organelles. Mitochondria and chloroplasts are autonomous (somewhat independent) organelles that grow and reproduce within the cell.  Clinical Correlation: Mitochondrium MERRF syndrome (Myoclonic Epilepsy with Ragged Red Fibers) is a rare mitochondrial disease. Multisystem disorder characterized by myoclonus (often the first symptom) followed by generalized epilepsy, ataxia, weakness, and dementia. Symptoms usually first appear in childhood or adolescence after normal early development. The diagnosis is based on clinical features and a muscle biopsy finding of ragged red fibers. From: https://rarediseases.info.nih.gov/diseases/7144/myoclonic-epilepsy-with-ragged-red-fibers Clinical Relation: Mitochondrium  Peroxisomes Peroxisomes are specialized metabolic compartments bounded by a single membrane Peroxisomes produce hydrogen peroxide and convert it to water Oxygen is used to break down different types of molecules (e.g. fatty acids) and send them to mitochondria for fuel (function in catabolism of long fatty chains.) Peroxisomes in the liver detoxify alcohol and other harmful compounds by transferring hydrogen from the poisons to oxygen. Chloroplast Peroxisome Mitochondrion 1 µm  Clinical Correlation: Peroxisome The peroxisomal disorders represent a group of genetic diseases which there is an impairment in one or more peroxisomal functions. Zellweger syndrome belongs to a group of diseases called peroxisome biogenesis disorders (PBD). The diseases are caused by defects in any one of the PEX genes that are required for the normal formation and function of peroxisomes. Peroxisomes are required for normal brain development and function and the formation of myelin, the whitish substance that coats nerve fibers. They also are required for normal eye, liver, kidney, and bone functions.  Clinical Correlation: Peroxisome The Zellweger spectrum disorders result from dysfunctional lipid metabolism, including the over-accumulation of very long-chain fatty acids and phytanic acid, and defects of bile acids and plasmalogens--specialized lipids found in cell membranes and myelin sheaths of nerve fibers.  Centrosome – Centrioles In animal cells, microtubules grow out from a centrosome, a region that is often located near the nucleus and is considered a “microtubule-organizing center.” These microtubules function as compression-resisting girders of the cytoskeleton. Before an animal cell divides, the centrioles replicate. Although centrosomes with centrioles may help organize microtubule assembly in animal cells, they are not essential for this function in all eukaryotes (not present in fungi and plant cells). Within the centrosome is a pair of centrioles, each composed of nine sets of triplet microtubules arranged in a ring.  can also be disassembled and their tubulin used to build mi- crotubules elsewhere in the cell. Because of the orientation Centrosome of tubulin dimers, the two ends of a microtubule are slightly different. One end can accumulate or release tubulin dimers at a much higher rate than the other, thus growing and shrinking significantly during cellular activities. (This is called the “plus end,” not because it can only add tubulin proteins but because it’s the end where both “on” and “off” Microtubule rates are much higher.) Centrosome – Microtubules shape and support the cell and also serve as tracks along which organelles equipped with motor proteins Centrioles Centrioles can move. In addition to the example in Figure 6.21, micro- 0.25 µm tubules guide secretory vesicles from the Golgi apparatus to the plasma membrane. Microtubules are also involved in the separation of chromosomes during cell division, which will be discussed in Chapter 12. Centrosomes and Centrioles In animal cells, microtubules grow out from a centrosome, a region that is often located near the nucleus and is considered a “microtubule-organizing center.” These microtubules function as compression-resisting girders of the cytoskeleton. Within the centrosome is a pair of centrioles, each composed of nine sets of triplet microtubules arranged in a ring (Figure 6.22). Before an animal cell divides, Longitudinal section Microtubules Cross section the centrioles replicate. Although centrosomes with centrioles of one centriole of the other centriole References & Thank You…