Module 3.4 Cytoplasmic Organelles

MODULE 3.4 CYTOPLASMIC ORGANELLES

© 2016 Pearson Education, Inc. Cytoplasmic Organelles • Organelles are cellular machinery with specific functions vital to maintaining homeostasis; some are separated from cytosol by membrane while others are not enclosed in a membrane (Figure 3.15) • Membrane-bound include: mitochondria, peroxisomes, endoplasmic reticulum, Golgi apparatus, and lysosomes • Organelles that are not enclosed in membrane include: ribosomes and centrosomes

Mitochondria (Figures 3.16, 3.17; Table 3.2); “power plant” of cell; membrane-bound organelles involved in energy production; provide majority of ATP used in cell: • Each mitochondrion has its own DNA, enzymes, and ribosomes (organelle involved in protein synthesis) • Membrane is double bilayer structure with smooth outer membrane and inner membrane that is highly folded into cristae

Figure 3.16 Structure of the mitochondrion. © 2016 Pearson Education, Inc. Mitochondria • Each membrane has its own unique enzymes and proteins required to perform specific functions (Figure 3.17): • Outer membrane – large channels that allow molecules from cytosol to enter intermembrane space (space between two membranes) • Inner membrane – more selective; essentially impermeable to most solutes except those for which it has specific transport proteins; as a result matrix (innermost space) contains DNA, mitochondrial proteins, and enzymes • Matrix contains enzymes and proteins that break down organic fuels via a series of reactions called oxidative catabolism

Peroxisomes – membrane- bound organelles • Use oxygen to carry out variety of reactions, one of their main reactions uses oxygen to produce hydrogen peroxide (H2O2); hydrogen peroxide along with oxidative enzymes perform various functions: • 1. Oxidizing toxic substances-Converts toxic chemicals into less toxic compounds which are then eliminated from the body • 2. Break down fatty acids • 3. Synthesizing certain phospholipids-critical components of plasma membrane

• Ribosomes (Table 3.2); tiny granular nonmembrane-bound organelles where protein synthesis takes place • Composed of large and small subunits; each made of ribosomal proteins and ribosomal RNA (rRNA) • Can be free or bound, structurally identical (only differ in location) • Free-suspended in cytosol; make proteins mainly used in cytosol itself • Bound-Are associated with the membranes of other cellular structures, all start out free, but some attach themselves to the endoplasmic reticulum or nuclear envelope, typically make proteins that will be exported from the cell, transported to certain organelles such as lysosomes, or inserted into membrane

The Endomembrane System (Figures 3.19, 3.20, 3.21; Table 3.2): • Form vesicles that exchange proteins and other molecules; Organelles that transfer molecules in this manner are part of a system called the endomembrane system, whose components together synthesize, modify, and package molecules produced within cell

© 2016 Pearson Education, Inc. The Endomembrane System The Endomembrane System (Figures 3.19, 3.20, 3.21; Table 3.2) (continued): • Plasma membrane, nuclear envelope, and following organelles are components of the system (Figure 3.19): • Endoplasmic reticulum (ER) • Rough endoplasmic reticulum (RER) • Smooth endoplasmic reticulum (SER) • Golgi apparatus • Lysosomes

Endoplasmic reticulum (ER) – large, folded membrane surrounding nucleus, highly-folded phospholipid bilayer continuous with the nuclear envelope; 2 distinct regions of ER membrane-rough ER (RER) has ribosomes bound to it and smooth ER (SER) does not

Table 3.2 Cytoplasmic Organelles. © 2016 Pearson Education, Inc. • Recall that proteins must be folded into their proper shape before they become functional. Yet ribosomes, the sites of protein synthesis only assemble amino acids into a polymer called a polypeptide (the protein’s primary structure) without a three-dimensional shape. So, ribosomes by themselves do not synthesize fully functional proteins.

© 2016 Pearson Education, Inc. The Endomembrane System Rough endoplasmic reticulum – ribosomes bound to membrane, the polypeptides synthesized pass through the RER membrane into its lumen, where enzymes catalyze reactions that FOLD polymers into their correct 3-dimensional shapes. • RER recognizes proteins that have folded into incorrect shape and sends them to be degraded. • Many proteins that enter RER to be folded are destined for export from the cell • When a secretory protein is fully assembled, it leaves RER packaged in a small, membrane-bounded structure called a transport vesicle.

© 2016 Pearson Education, Inc. The Endomembrane System Smooth endoplasmic reticulum (SER) – not associated with ribosomes; essentially no role in protein synthesis; performs following vital functions: • Stores calcium ions • Detoxification reactions; limits damage caused by certain substances • Lipid synthesis- Synthesizes the bulk of cells lipid membrane components

Golgi apparatus – located between RER and plasma membrane – group of flattened membranous sacs filled with enzymes and other molecules (Figure 3.20) • Proteins and lipids made by ER are further modified, sorted, and packaged for export in the Golgi • Products packaged in Golgi can be secreted from cell by exocytosis, become part of the plasma membrane, or sent to the lysosome

• The RER recognizes and helps dispose of misfolded proteins, but sometimes the RER’s selectivity can actually be detrimental as in the case with some forms of cystic fibrosis.s • Certain cells are missing a protein that forms a chloride ion channel in plasma membrane • Causes deficient chloride ion transport that impacts ion and water secretions in lungs, digestive and integumentary systems; results in abnormally thick mucus; blocks airways, digestive enzyme deficiencies, and very salty sweat • DNA mutation causes chloride channel protein to misfold slightly in RER; protein therefore destroyed even though it would generally be functional if inserted into membrane • In short, disease is caused by “overprotective” RER

Lysosomes – organelles responsible for digestion of worn out cell components, or whole cells in some cases: • Contain enzymes called acid hydrolases • Macromolecules are broken down into smaller subunits that can be released to cytosol for disposal or for use in protein synthesis and various metabolic reactions

Figure 3.21 Function of the endomembrane system. © 2016 Pearson Education, Inc. Lysosomal Storage Diseases • Group of diseases resulting from deficiency of one or more acid hydrolases of lysosomes; examples include: • Gaucher’s disease – deficiency causes accumulation of glycolipids in cells of blood, spleen, liver, lungs, bone, and sometimes brain; most severe form is fatal in infancy or early childhood • Tay-Sachs disease – glycolipids accumulate in brain lysosomes, leading to progressive neural dysfunction and death by age 4–5

© 2016 Pearson Education, Inc. Lysosomal Storage Diseases • Group of diseases resulting from deficiency of one or more acid hydrolases of lysosomes; examples include (continued): • Hurler syndrome – large polysaccharides accumulate in many cells (heart, liver, brain); death can result in childhood from organ damage • Niemann-Pick disease – lipids accumulate in lysosomes, affects spleen, liver, brain, lungs, and bone marrow; severe form causes organ damage and neural dysfunction

© 2016 Pearson Education, Inc. The Cytoskeleton Cytoskeleton – made of several types of protein filaments; dynamic structure able to change function based on needs of cell; plays a variety of critical roles: • Gives the cell its characteristic shape and size by creating an internal framework • Supporting the plasma and nuclear membranes as well as the organelles • Functioning in movement • Performing specialized functions in different cell types; for example, phagocytosis, contraction by muscle cells, and nerve cell long “arms” © 2016 Pearson Education, Inc. Types of Filaments

Cytoskeleton contains three types of long protein filaments; composed of smaller protein subunits that allow for rapid disassembly and reassembly • Actin filaments • Intermediate filaments • Microtubules

Actin filaments (microfilaments) are the thinnest filament in cytoskeleton; composed of two intertwining strands of actin subunits • Provide structural support, bear tension, and maintain cell’s shape • Involved in cellular motion when combined with the motor protein myosin

Table 3.3 Cytoskeletal Filaments. © 2016 Pearson Education, Inc. Types of Filaments Intermediate filaments – ropelike; made of diverse fibrous proteins including keratin, form more permanent structures in the cell Form much of framework of cell and anchor organelles in place • Form much of framework of cell and anchor organelles within it • Help organelles and nucleus maintain their shape and size • Help cells and tissues withstand mechanical stresses

Table 3.3 Cytoskeletal Filaments. © 2016 Pearson Education, Inc. Types of Filaments Microtubules – largest protein filaments in cytoskeleton; hollow rods or tubes composed of the protein subunits tubulins; can be rapidly added or removed allowing for size and shape changes within cell • Gives cell characteristic shape/size • Maintain internal architecture of cell • Associated with motor proteins called dynein and kinesin, move along microtubules like a train on a track, they carry their “cargo” to appropriate destinations

Table 3.3 Cytoskeletal Filaments. © 2016 Pearson Education, Inc. Types of Filaments Microtubules extend out from centrosome (consists of a gel matrix containing tubulin proteins necessary for microtubule formation) (Figure 3.22) • When cell is not dividing, centrosome is a microtubule- organization center located close to nucleus • The centrosome also contains a pair of centrioles, composed of a ring of nine groups of three modified microtubules and other proteins, is critical for cellular division • Basal bodies – modified centrioles found on internal surface of plasma membrane where flagella and cilia sprout from © 2016 Pearson Education, Inc. Types of Filaments

Cytoskeleton forms the inner framework of cell surface extensions in many cells, these extensions include: • Microvilli • Cilia • Flagella

• Microvilli • Plasma membrane folded into tiny finger-like extensions Structure-Function Core Principle • Increase surface area of cells in organs specialized for absorption

• Cilia • Larger than microvilli • Hairlike projections composed of microtubules and motor proteins, enable cilia to be motile • Coordinated beating motion sweeps substances past the cell (Table 3.4) • Ex, cells that line our respiratory passages have cilia

Table 3.4 Cilia and Flagella. © 2016 Pearson Education, Inc. Cellular Extensions • Flagella • Solitary; long extension from cell, move in whiplike motion to propel whole cell • Same internal structure as cilia • Found only on sperm cells

Figure 3.24 Structure of cilia and flagella (only cilium shown here). © 2016 Pearson Education, Inc. Primary Ciliary Dyskinesia • Rare genetic disorder characterized by defect in one or more protein components of cilia and flagella • Affects many types of cells: respiratory passage linings, middle ear, uterine tubes (females), sperm (males) • Leads to buildup of mucus in lungs; increases risk of infection; commonly progressive damage to lungs • May experience repeated ear infections can lead to hearing loss • Males may be infertile due to lack of sperm motility

© 2016 Pearson Education, Inc. The Nucleus Nucleus – the biosynthetic center of the cell that contains the cell’s DNA and much of its RNA(Figure 3.25): • DNA housed in nucleus contains code or plans for nearly every protein in body • These plans (genes) within DNA are used by several different kinds of RNA to build the proteins for our cells. Nucleus in large part determines the type of proteins the cell makes and the rate which they are made.

© 2016 Pearson Education, Inc. The Nucleus Nucleus consists of three main structures: • Nuclear envelope – enclosing membrane composed of a phospholipid bilayer, double membrane, the two membranes are joined at large protein complexes that produce nuclear pores (connect cytoplasm with nucleoplasm, allow substances to move between the two) • DNA and associated proteins • Nucleolus- “ribosome factory”

Figure 3.26 The nuclear pore. © 2016 Pearson Education, Inc. Chromatin and Chromosomes Chromatin – consists of one extremely long DNA molecule and its associated proteins; organize and fold molecule to conserve space (Figure 3.27a): • Nucleosome – strand of DNA coiled around a group of histone proteins; appears like beads on a string • Reduces length of strand by about one-third

During periods of cell division, chromatin threads coil tightly and condense into thick structures called chromosomes (Figure 3.27b): • Most human cells contain two sets of 23 chromosomes (46 total), (one set of 23 from each parent) maternal and paternal chromosomes are called homologous chromosomes • Sister chromatids – paired and identical copies of a chromosome; made in preparation for cell division; connected to one another at region called centromere

• Nucleoli: (singular – nucleolus)- “ribosome factory” region in nucleus where ribosomes are assembled

© 2016 Pearson Education, Inc. Protein Synthesis Protein synthesis – process of manufacturing proteins from DNA blueprint using RNA • Gene expression – production of protein from specific gene • Two processes actually make a specific protein: • Transcription – process where the code specified by a gene is copied; creating messenger RNA (mRNA) • Translation-ribosomes read the nucleotide sequence of the mRNA and synthesize a polypeptide chain containing the correct amino acid sequence. DNATranscriptionmRNATranslationProtein

© 2016 Pearson Education, Inc. Genes and the Genetic Code • Genes – segments of DNA, most of which specify amino acid sequences of proteins. • 4 different nucleotides in DNA (A,T, G, C); each set of 3 nucleotides (called triplet) represents a different amino acid; each amino acid may be represented by more than one triplet • During transcription each DNA triplet is transcribed into a complementary three-nucleotide sequence of mRNA called a codon

• During translation, the tRNA has a region called the anticodon, which contains a sequence of 3 nucleotides that is complementary to a specific mRNA codon.

• Genetic code – list of which amino acid is specified by each DNA triplet (Figure 3.28 on next slide)

• Mutations – changes to DNA, can be due to mistakes in copying DNA or induced by agents called mutagens • Common mutagens include ultraviolet light and other forms of radiation, chemicals such as benzene, and infection with certain viruses • DNA mutations are the basis for many diseases, including cancer

© 2016 Pearson Education, Inc. Toxicity of the “Death Cap” Mushroom • Amanita phalloides (and other Amanita) are responsible for 95% of mushroom-related fatalities worldwide • A. phalloides is tasty and resembles many nontoxic mushrooms; main toxin inhibits RNA polymerase; prevents formation of new strands of mRNA • Essentially stops protein synthesis and disrupts many cell functions, leading to cell death • No antidote exists, although some have shown promise • Liver suffers most damage; patients who survive generally require a liver transplant

© 2016 Pearson Education, Inc. Transcription • Transcription (Figure 3.29): process of making mRNA copy of DNA (transcript) that can exit the nucleus and enter the cytosol. • Transcript is built with help of the enzyme RNA polymerase the cells “Copy Machine”, when it binds to a gene; brings in complementary nucleotides one at a time (nucleotides that are complementary to the DNA strand) linking them together to form mRNA • Transcription proceeds in 3 general stages (Figure 3.29): • Initiation-beginning of transcription • Elongation-when nucleotides are linked in a specific order • Termination-end of transcription © 2016 Pearson Education, Inc. Transcription • Initiation – beginning of transcription, begins when protein transcription factors bind to the promoter, segment near the gene on template strand of DNA; RNA polymerase then binds to promoter; DNA unwinds with aid of enzyme helicase

• Elongation – process where RNA polymerase builds a complementary mRNA transcript with free nuclotides

• Termination – transcription ends when the end of gene is reached and mRNA transcript is released. • After transcription, the transcript is called pre-mRNA, it is not ready to be sent out to cytosol because it must first be modified in several ways.

• Remember, after transcription, the transcript (pre-mRNA) isn’t ready; must first be modified in several ways • Noncoding sections of a gene called introns; exons contain actual code, introns in pre-mRNA must be removed and exons spliced together before final mRNA transcript is sent to cytosol (this step is called RNA processing)

• When processing is complete, the mRNA exits the nucleus through a nuclear pore, enters cytosol, ready for translation.