Membrane-Bound Organelles PDF

WHAT DIS-EASE? GUESS THE DISEASE BEING ACTED OUT BY THE PERFORMER BASED ON CLUES PROVIDED THROUGH GESTURES, FACIAL EXPRESSIONS, AND MOVEMENTS. MEMBRANE-BOUND ORGANELLES Overview of Key Cellular Organelles and Processes  LEARNING OBJECTIVES 1. Identify the functions of key membrane-bou...

WHAT DIS-EASE? GUESS THE DISEASE BEING ACTED OUT BY THE PERFORMER BASED ON CLUES PROVIDED THROUGH GESTURES, FACIAL EXPRESSIONS, AND MOVEMENTS. MEMBRANE-BOUND ORGANELLES Overview of Key Cellular Organelles and Processes  LEARNING OBJECTIVES 1. Identify the functions of key membrane-bound organelles and their roles in the cell 2. Explain how membrane-bound organelles handle protein synthesis, modification, and transport MEMBRANE-BOUND ORGANELLE Key Focus: Endoplasmic Reticulum , Golgi apparatus, lysosomes, and peroxisomes Membrane Bound organelle functions a.Translational b. post translational modifcation c. protein transport d. membrane flow and sorting (trafficking) ENDOPLASMIC RETICULUM SMOOTH ENDOPLASMIC RETICULUM (SER) The smooth endoplasmic reticulum (SER) is a network of tube-like structures within cells. Unlike rough ER, it lacks ribosomes on its surface, which give it a "Smooth"appearance. FUNCTION:.Lipid synthesis Steroid Hormone prodution Detoxyfication ROUGH ENDOPLASMIC RETICULUM (RER) Rough ER is named for its rough appearance, which is due to the ribosomes attached to its outer (cytoplasmic) surface. Rough ER lies immediately adjacent to the cell nucleus, and its membrane is continuous with the outer membrane of the nuclear envelope. FUNCTION: Protein synthesis Protein Folding and Modification Quality Control Transport to Golgi Apparatus MEDICAL APPLICATION OF ENDOPLASMIC RETICULUM LIVER INJURY THE LIVER'S ER AND UPR ARE KEY PLAYERS IN RESPONDING TO VARIOUS STRESSORS. WHILE EXCESSIVE ER STRESS CAN LEAD TO LIVER DISEASES, IT CAN ALSO BE HARNESSED TO INDUCE CELL DEATH IN SPECIFIC CONTEXTS. BY UNDERSTANDING THE MECHANISMS UNDERLYING ER STRESS- INDUCED CELL DEATH, RESEARCHERS MAY DEVELOP NOVEL THERAPEUTIC STRATEGIES TO TARGET LIVER DISEASES LIKE VIRAL HEPATITIS, FATTY LIVER DISEASE, AND LIVER CANCER. MEDICAL APPLICATION OF ENDOPLASMIC RETICULUM Protein Folding Disorders THE ROUGH ENDOPLASMIC RETICULUM (RER) IS CRUCIAL FOR PROTEIN SYNTHESIS AND FOLDING. MISFOLDED PROTEINS CAN CONTRIBUTE TO DISEASES LIKE ALZHEIMER'S AND PARKINSON'S. RESEARCH ON THE UNFOLDED PROTEIN RESPONSE (UPR) IN THE ER IS ESSENTIAL FOR DEVELOPING THERAPIES THAT IMPROVE PROTEIN FOLDING OR ELIMINATE MISFOLDED PROTEINS. WHAT DISEASES ARE ASSOCIATED WITH THE ENDOPLASMIC RETICULUM?  ALZHEIMER'S DISEASE In Alzheimer's, the accumulation of amyloid-beta plaques and tau tangles, both misfolded proteins, triggers ER stress in neurons. This leads to neuronal dysfunction and death.  PARKINSON'S DISEASE Parkinson's involves the accumulation of misfolded alpha- synuclein protein in neurons. This triggers ER stress, leading to cell death in the substantia nigra, a brain region crucial for movement control.  ATHEROSCLEROSIS Atherosclerosis is a condition where fatty deposits called plaques build up on the walls of arteries, leading to narrowed arteries and reduced blood flow. When the ER is stressed due to factors like high cholesterol, inflammation, or oxidative stress, it can't properly fold proteins. This leads to a buildup of misfolded proteins, triggering a response called the unfolded protein response (UPR). Chronic ER stress and UPR activation can cause inflammation, cell death, and contribute to the formation and progression of atherosclerotic plaques  AUTOIMMUNE DISEASES Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are linked to several autoimmune diseases. When the ER is stressed due to factors like genetic mutations or environmental triggers, it can lead to abnormal immune responses1. This can result in the body attacking its own tissues, causing autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes THE GOLGI APPARATUS STRUCTURE OF THE GOLGI APPARATUS  Parts Importance Function cis face is essential for maintaining cellular Cisface organization and function. proper cellular operation and the maintenance of homeostasis packaging, modification, and transport functions sorting proteins and lipids that are received (at the cis face) or Cisternae for the cell overall. released (at the trans face) by the organelle transport proteins and lipids from the endoplasmic reticulum to Incoming transport maintaining cellular organization and facilitating the Golgi apparatus, facilitate membrane fusion for content delivery, enable processing and modification of biomolecules, sort vesicle the proper functioning of biological processes. and distribute cargo to specific cellular locations, and mediate cellular communication by transporting signaling molecules. lumen functions as a specialized internal compartment where lumen is crucial for processing and folding proteins are processed and folded, lipids are synthesized, and proteins, storing ions and small molecules, and Lumen facilitating biochemical reactions essential for biochemical reactions occur, contributing to the overall functionality of organelles like the endoplasmic reticulum and cellular function and homeostasis. Golgi apparatus.  Parts Importance Function they facilitate the transport of proteins and lipids Newly forming between organelles, ensuring proper cellular to encapsulate and transport proteins and lipids from one communication and the timely delivery of organelle to another, enabling the efficient delivery of cargo for vesicle essential materials necessary for various processing, modification, and secretion within the cell. metabolic processes it ensures the accurate sorting and distribution to sort and package modified proteins and lipids for delivery to of proteins and lipids, plays a crucial role in the their final destinations, whether within the cell or for secretion secretion of substances, and maintains cellular Transface organization by directing materials to their outside the cell. It also facilitates the formation of transport vesicles that carry these materials to various organelles or the appropriate cellular locations, thereby plasma membrane. supporting essential physiological functions. they transport proteins and other molecules from the Golgi apparatus to the plasma to transport and release proteins and other molecules from the membrane for secretion, playing a crucial role in Golgi apparatus to the plasma membrane, where they can be Secretory vesicle processes such as hormone release, secreted outside the cell or delivered to specific cellular locations, neurotransmitter signaling, and the delivery of enabling processes such as hormone secretion, enzymes, thereby facilitating communication and neurotransmission, and extracellular matrix production. functionality within and between cells. MEDICAL APPLICATIONS OF GOLGI APPARATUS Cancer diagnosis The expression levels of some Golgi-associated proteins, such as GOLPH3, RAB1B, and GOLM1, are correlated with cancer survival and may be used as biomarkers. WHAT DISEASES ARE ASSOCIATED WITH THE GOLGI APPARATUS? Structural and functional changes of the Golgi apparatus are associated with several neurodegenerative diseases, such as Amyotrophic lateral sclerosis Huntington's disease Creutzfeldt-Jacob disease Multiple system atrophy Amyotrophic lateral sclerosis The Golgi apparatus in ALS patients' motor neurons frequently appears either weakened, meaning that its membrane content has decreased, or fragmented, meaning that it has been broken up into several disjointed parts or tubular-vesicular clusters (Mourelatos et al., 1990; Gonatas et al., 1992). All varieties of motor neurons found in the brainstem, spinal cord, and cerebral cortex exhibit these pathogenic alterations (Mourelatos et al., 1996; Fujita et al., 1999, 2000). Huntington's disease The Golgi apparatus is a sensor of cellular stress and signals through the Golgi stress response. In HD, the Golgi stress response appears to follow distinct pathways from other neurological disorders. Creutzfeldt-Jacob disease The Golgi apparatus (GA) and trans-Golgi network (TGN) in cortical ballooned neurons of patients with CJD show fragmentation. This fragmentation is an early event in the disease's pathological cascade and precedes other pathological changes in the neuron. LYSOSOMES  Parts Importance Function Encloses the lysosome Acts as a barrier to separate Plasma Membrane and maintains its distinct lysosomal contents from the internal environment. cytoplasm. Lipid Bilayer Composed of phospholipids that form the basic structure Provides fluidity and flexibility of the lysosomal membrane. to the lysosomal membrane Essential for cellular waste Engages in autophagy to Hydrolytic Enzyme Mixture disposal and recycling of recycle damaged organelles cellular components. and proteins. Protect lysosomal Involved in signaling pathways Glycosylated enzymes from degradation Membrane Transport that regulate lysosomal by providing a protective functions and cellular Protein glycan shield responses. Medical Application of Lysosomes Cancer Treatment Immunotherapy Diagnostics Cancer Treatment Recent research has identified lysosomes as a promising target in cancer treatment due to their unique roles in cell death and metabolism.  Immunotherapy A cancer cell– targeted molecularly imprinted lysosomal nanodegrader (MILND) for boosting immune checkpoint blockade therapy against tumors What is Lysosomal Storage Disease? Types of Lysosomal Storage Diseases Gaucher disease Fabry disease Pompe disease GAUCHER DISEASE Gaucher disease is a genetic disorder linked to lysosomal storage dysfunction. It results from mutations in the GBA gene, which encodes an enzyme called glucocerebrosidase.  FABRY DISEASE This disease results from a mutation in the GLA gene, which encodes the enzyme alpha-galactosidase A.  POMPE DISEASE Pompe disease, also known as glycogen storage disease type II, is a rare, inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells PEROXISOME  Membrane Transportation protein Plasma membrane Matrix Hydrolytic Lipid bilayer enzyme mixtures  Parts Importance Function Essential for the import Facilitate the transport of enzymes Membrane of proteins and lipids into and other proteins from the cytosol Trasnportation Protein the peroxisome into the peroxisomal matrix Provides structural integrity Maintains the environment necessary Plasma membrane and separates peroxisomal for enzyme activity and protects contents from the cytoplasm. against cytoplasmic interference. Contains a variety of Houses enzymes for oxidation Matrix enzymes crucial for reactions, including those that metabolic processes. produce hydrogen peroxide (H₂O₂) and catalase to decompose it. Important for breaking Catalyze oxidative reactions, Hyrodlytic enzymes down various substrates, converting harmful substances into mixtures including fatty acids and less toxic forms (e.g., converting toxic compounds. H₂O₂ to water).  HOW PEROXISOME LOCATION INFLUENCES CELLULAR FUNCTION? Medical Application of Peroxisome Detoxification Therapeutic targets Anti-Aging Therapies What is Peroxisomal Disease? Types of Peroxisomal Diseases X-linked Adrenoleukodystrophy (ALD) Zellweger Syndrome (ZS) Neonatal Adrenoleukodystrophy (NALD) X-linked Adrenoleukodystrophy (ALD) X-linked Adrenoleukodystrophy (ALD) is a genetic disorder that primarily affects males and is characterized by the breakdown of myelin Zellweger Syndrome (ZS) Zellweger Syndrome (ZS) is a rare, inherited disorder that affects various systems in the body, particularly the brain, liver, and kidneys. Neonatal Adrenoleukodystrophy (NALD) Neonatal Adrenoleukodystrophy (NALD) is a severe, genetic disorder characterized by early-onset neurological dysfunction and adrenal insufficiency. MEMBRANE-BOUND ORGANELLES FUNCTIONS  Membrane-bound organelles are specialized structures within a cell. They work together to make sure the cell functions smoothly, especially when it comes to creating, modifying, and transporting proteins and other molecules. Membrane- bound Organelle Transcription the process of gene expression, where the information in DNA is copied into mRNA. Translation the cellular process where proteins are synthesized from mRNA instructions.  TRANSLATION the two main stages of gene expression the process through which cells read the genetic code on messenger RNA (mRNA) takes place in the cytoplasm and involves the ribosome, tRNA (transfer RNA), TRANSLATION The ribosome, an organelle made up of rRNA (ribosomal RNA), attaches to the mRNA strand at a specific sequence called the start codon. emphasizes the function of the Rough Endoplasmic Reticulum (ER) in protein production. TRANSLATION small and large subunits of the ribosome assemble around the mRNA TRANSLATION tRNA molecules carry specific amino acids and have an anticodon that matches a codon on the mRNA setting the stage for the amino acid sequence to begin TRANSLATION the ribosome moves along the mRNA strand, reading each codon and matching it with the amino acid carried by tRNA. TRANSLATION The ribosome disassembles, and the polypeptide chain is now ready to undergo  Post- Translational Modification POST-TRANSLATIONAL MODIFICATION (PTM) REFERS TO COVALENT CHANGES TO PROTEINS AFTER THEIR SYNTHESIS PTMS REGULATE PROTEIN FUNCTIONS, AFFECTING ASPECTS SUCH AS FOLDING, ACTIVITY, STABILITY, LOCALIZATION, AND SIGNAL TRANSDUCTION Post-Translational Modification Phosphorylation Proteolysis Glycosylation Methylation Ubiquitination  Post-Translational Modification Phosphorylation The addition of phosphate groups to specific amino acids (usually serine, threonine, or tyrosine) by enzymes called kinases. This often activates or deactivates protein functions.  Abnormal phosphorylation of specific neural proteins may contribute to the development of Alzheimer's disease National Center for Biotechnology Information. (2007). Understanding the Human Genome Project. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK27949/  Post-Translational Modification Methylation The transfer of one-carbon methyl groups to nitrogen or oxygen to amino acid side chains increases the hydrophobicity of the protein and can neutralize a negative amino acid charge when bound to carboxylic acids. Methylation is mediated by methyltransferases and S-adenosyl methionine (SAM) is the primary methyl group donor  DNA methylation is a pivotal mechanism that influences gene expression and has significant implications for various diseases Cancer atherosclerosis Prader-willi Smith, J. (2023, October 1). The impact of DNA methylation on health. Health Research Journal  Protein glycation reactions leading to AGEs are thought to be the major causes of different diabetic complications Diabetes https://pmc.ncbi.nlm.nih.gov/articles/PM C3951818/  Post-Translational Modification Glycosylation Glycosylation is the addition of carbohydrate molecules to the polypeptide chain and modifying it into glycoproteins. Many of the proteins that are destined to become a part of plasma membrane or to be secreted from the cell, have carbohydrate chains attached to the amide nitrogen of asparagine(N linked) or the hydroxyl groups of serine, threonine(O linked). N glycosylation occurs in ER and O glycosylation occurs in the golgi complex.  Post-Translational Modification Proteolysis As the newly synthesized protein is released in the lumen of the ER, signal peptidases cleave peptide sequence. Apart from signal peptide, some polypeptide sequence of the protein is also cleaved resulting in the final sequence  The role of proteolysis in Alzheimer's disease https://pubmed.ncbi.nlm.nih.gov/10849764/ WHAT AM I ?  THEY ARE MADE UP OF HUNDREDS OR THOUSANDS OF SMALLER UNITS CALLED AMINO ACIDS, WHICH ARE ATTACHED TO ONE ANOTHER IN LONG CHAINS. ALSO, THEY’RE LARGE, COMPLEX MOLECULES THAT PLAY MANY CRITICAL ROLES IN THE BODY. THEY DO MOST OF THE WORK IN CELLS AND ARE REQUIRED FOR THE STRUCTURE, FUNCTION, AND REGULATION OF THE BODY’S TISSUES AND ORGANS. carbohydrates lipids protein TWO DIFFERENT TYPES OF PROTEIN TRANSPORT PROTEIN TRANSPORT PROTEINS facilitate the movement of various substances across cell membranes 2 TYPES OF PROTEIN TRANSPORT How Do They Work? EXAMPLE OF ACTIVE TRANSPORT VESICULAR TRANSPORT  MEMBRANE FLOW AND SORTING (TRAFFICKING)  Membrane Flow and Sorting (Trafficking) Membrane flow and sorting involve the movement and distribution of proteins and lipids within the cell, ensuring they reach the correct locations. This ensures that they reach the correct destination, either inside the cell or outside This involves the formation, transportation, and fusion of vesicles. VESICLE FORMATION Proteins are packaged into vesicles in the ER or Golgi. VESICLE TRANSPORT Vesicles move along the cytoskeleton to reach different parts of the cell. This requires molecular motors like kinesin. FUSION WITH TARGET MEMBRANES Vesicles fuse with the target membrane (e.g., lysosome, cell membrane), delivering their content  SORTING AND TARGETING proteins are sorted based on specific molecular tags (e.g., glycosylation patterns) that direct them to their final destinations. Some proteins are tagged for transport to the plasma membrane, while others are directed to lysosomes for degradation or to other organelles. RECYCLING Old or misdirected proteins are returned to the Golgi or ER for reuse or degradation ENDOCYTOSIS AND EXOCYTOSIS Endocytosis brings substances into the cell by engulfing them in vesicles, while exocytosis releases them out of the cell. PROTEIN TRAFFICKING Vesicle mediated trafficking Involves proteins made in the Endoplasmic reticulum ribosome Non vesicle mediated trafficking invloves protein made in free or cytosolic ribosome Three main coat proteins COPI vesicles transport vesicles from the cis-Golgi to the ER. This is known as retrograde transport. COPII vesicles transport vesicles from the ER to the cis-Golgi. This is known as anterograde transport. Clathrin mediated vesicles transport vesicles from the plasma membrane to the lysosome and from the Golgi to the lysosome. Protein Targeting Molecules Once proteins enter the endoplasmic reticulum and golgi, they are modified by chemical reactions called glycosylations. These reactions attach carbohydrate monomers to certain amino acids in proteins. These modifications are essential for both proper functioning of the final protein and targeting of the protein to the correct location. Vesicular Secretory Pathways Once protein with the appropriate targeting molecules reach the Golgi, they are modified and prepared for secretion via a process called exocytosis. There are two pathways of protein secretion; constitutive secretion - vesicles are undergoing exocytosis regulated secretion - loaded vesicles are stored in cytosol until a release signal is received. Proteins with no targeting molecule undergo constitutive secretion, This is the deafult pathway SUMMARY There are two main pathways of protein trafficking; vesicle mediated trafficking and non-vesicle mediated trafficking. Vesicle mediated trafficking involves coat proteins called COPI, COPII and Clathrin. I-cell disease is caused by a loss of the lysosomal targeting molecule. Non-vesicle mediated trafficking requires amino acid sequences to target proteins to their destination.  SUMMARY How Membrane- Bound Organelles Work Together? https://www.slideserve.com/erussel/tour-of-the-cell-1-powerpoint- ppt-presentation IMPORTANCE IN CELL AND MOLECULAR BIOLOGY Membrane-bound organelles are crucial for organizing and compartmentalizing cellular functions, ensuring efficiency and specialization within eukaryotic cells. They are central to protein synthesis, modification, and transport, facilitating cell communication and growth. These organelles manage waste breakdown, detoxification, and energy production, maintaining cellular health and stability. Understanding their roles is essential in cell and molecular biology as they regulate gene expression, signaling, and metabolic pathways. Dysfunction in membrane-bound organelles is linked to numerous diseases, highlighting their importance in research and medicine.  1. Which organelle is involved in the synthesis of proteins, where mRNA is translated into QUIZ polypeptide chains? 2. Which organelle is responsible for modifying proteins after synthesis by adding sugars and other molecules, preparing them for their final Match each question with roles? the correct organelle and 3. Which organelle assists in moving proteins to the specific process it is their specific destinations within or outside of involved in. the cell? Choose the appropriate 4. Which organelle is involved in the transport of organelle that corresponds cellular waste proteins to be degraded and to each described function. recycled? 5. Which organelle helps sort and direct proteins within the cell by packaging them into vesicles for delivery to various cellular locations?