Cell Biology: The Nucleus

Nucleus

• The nucleus is the control center of the cell, containing DNA and responsible for crucial cellular functions like DNA replication and transcription.
• It’s surrounded by a double-layered membrane known as a nuclear envelope with an outer layer and an inner layer.
• Nuclear Envelope:
  • The outer layer has ribosomes attached to it, facilitating the movement of mRNA from the nucleus to the cytoplasm.
  • The inner layer has lamin proteins that help control the shape of the nuclear envelope, interact with chromatin, and play a role in cell division.
  • The nuclear pores, embedded in the nuclear envelope, allow selective transport of molecules like ions, proteins, and nucleotides between the cytoplasm and nucleus.
• Nucleolus:
  • Found inside the nucleus, responsible for rRNA synthesis.
  • rRNA combines with proteins to form ribosomes.
• Chromatin:
  • A complex of DNA and proteins, primarily histones, that forms chromosomes.
  • Euchromatin: Loose, actively transcribed chromatin, often found in the center of the nucleus, facilitates gene expression and DNA replication.
  • Heterochromatin: Dense, tightly packed chromatin, located near the inner nuclear membrane, less active in transcription and replication.

Endoplasmic Reticulum

• Rough ER:
  • Network of interconnected membrane-bound sacs and tubules.
  • Has ribosomes attached to its outer membrane.
  • Involved in protein synthesis, specifically for proteins destined for lysosomes, cellular membranes, or secretion.
  • Helps fold proteins and modify them by adding sugar residues (glycosylation).
  • Packages proteins into vesicles for transport to the Golgi apparatus.
• Smooth ER:
  • Continuous with the rough ER but lacks ribosomes.
  • Primarily associated with lipid synthesis, producing fatty acids, phospholipids, and cholesterol.
  • Contains enzymes like CYP450 crucial for detoxification of drugs, toxins, and alcohol via biotransformation.
  • Plays a role in glucose 6-phosphate metabolism.
  • Stores calcium ions, important in muscle contraction and other cellular processes.

Golgi Apparatus

• Stacks of flattened, membrane-bound compartments (cisternae).
• Plays a key role in sorting, modifying, and packaging proteins and lipids.
• Receives vesicles containing proteins and lipids from the rough ER and smooth ER.
• Cis Golgi: The receiving side of the Golgi apparatus, where vesicles enter.
• Trans Golgi: The shipping side of the Golgi apparatus, where modified proteins are packaged into new vesicles for delivery to their final destinations.
• Modifies proteins by adding sugars or other molecules, further processing them.
• Packages proteins into vesicles for transport to lysosomes, the cell membrane, or secretion.
• The Golgi apparatus is responsible for glycosylation reactions, specifically the O-type glycosylation, which involves adding a sugar residue to the oxygen component of a protein.
• The Golgi apparatus phosphorylates specific types of proteins, a process crucial for proper cell function and linked to diseases like eye cell disease.
• After glycosylation and phosphorylation, the Golgi packages molecules into vesicles.
• These vesicles transport modified proteins and lipids to their final destinations, which include lysosomes, cell membranes, and excretion out of the cell.

Cell Membrane

• The cell membrane is composed of a phospholipid bilayer, comprising a polar, hydrophilic head (phospholipid) and a non-polar, hydrophobic tail (fatty acids).
• Cholesterol is embedded within the phospholipid bilayer and controls membrane fluidity. Higher cholesterol levels decrease fluidity, while lower levels increase fluidity.
• Proteins within the cell membrane act as transporters, enzymes, and linker proteins between cells.
• The cell membrane functions as a selectively permeable barrier, allowing specific types of diffusion, including simple diffusion, facilitated diffusion, and vesicular transport.

Lysosomes

• Lysosomes are spherical organelles containing hydrolytic enzymes, including proteases, nucleases, lipases, and glucosidases.
• These enzymes break down macromolecules, such as proteins, nucleic acids, lipids, and carbohydrates, that are brought into the cell through phagocytosis or endocytosis.
• Lysosomes also participate in autophagy, the process of breaking down worn-out organelles (e.g., ribosomes) to recycle cellular components.
• Damaged cells undergo autolysis when lysosomes release their enzymes, leading to the breakdown of the cell's macromolecules.

Peroxisomes

• Peroxisomes are spherical organelles containing enzymes like catalase, oxidase, and other metabolic enzymes.
• Catalase and oxidase are essential for breaking down free radicals, particularly hydrogen peroxide, which accumulates during fatty acid metabolism.
• Peroxisomes perform fatty acid oxidation, breaking down fatty acids into acetyl-CoA molecules.
• Peroxisomes synthesize lipids, including cholesterol, and plasmalogen, a specific lipid essential for the white matter in the brain.
• Impaired peroxisome function can lead to decreased white matter production and neurological issues.
• Peroxisomes also contribute to small-scale ethanol metabolism.

Mitochondria

• Mitochondria are known as the "powerhouse of the cell" and are responsible for ATP synthesis, primarily through oxidative phosphorylation.
• The outer membrane of the mitochondria is smooth and highly permeable, while the inner membrane, known as the cristae, is less permeable.
• The mitochondrial matrix houses metabolic reactions and mitochondrial DNA.
• The electron transport chain, located on the inner membrane, drives oxidative phosphorylation and ATP production.
• Key metabolic reactions occurring within the mitochondria include the Krebs cycle, heme synthesis, the urea cycle, gluconeogenesis, and ketogenesis.
• Mitochondrial DNA is inherited from the mother and encodes proteins involved in metabolic processes.

Ribosomes

• Ribosomes are composed of two subunits: a large subunit (60S in eukaryotic cells) and a small subunit (40S in eukaryotic cells).
• Ribosomes consist of rRNA and proteins.
• Ribosomes can be found either bound to the rough endoplasmic reticulum (membrane-bound ribosomes) or freely in the cytosol (cytosolic or free ribosomes).
• Ribosomes are the sites of protein synthesis, where mRNA and tRNA work together to translate genetic information into proteins. This process is called translation.
• Ribosomes are composed of two subunits that sit together, a large and a small subunit.
• Ribosomes help to bind to mRNA and allow tRNA to attach to the mRNA.
• Ribosomes are involved in protein synthesis.
• Ribosomes attached to the Rough ER will produce integral/peripheral membrane proteins, lysosomal proteins, and proteins that will be excreted from the cell.
• Cytosolic ribosomes produce cytosolic proteins (enzymes and proteins that remain in the cell).

Cytoskeleton

• The cytoskeleton is comprised of a network of fibers that are found throughout the cell.
• The cytoskeleton helps to give the cell structure, maintain shape, and enables movement.

Microfilaments

• Microfilaments are composed of actin monomers that form a long polymer.
• Microfilaments are important for muscle contraction with the help of myosin.
• Microfilaments are important for cytokinesis - the formation of a constriction ring during mitosis.
• Microfilaments are important for diapedesis - the process in which white blood cells squeeze through capillaries.
• Microfilaments are important for phagocytosis - the process in which white blood cells consume pathogens.

Intermediate Filaments

• Intermediate filaments are strong, high-tensile filaments that are not very mobile.
• Intermediate filaments help to anchor the cell to the extracellular matrix.
• Intermediate filaments help to anchor cells to each other.
• Intermediate filaments help to anchor organelles within the cell.

Microtubules

• Microtubules are composed of alpha- and beta-tubulin that form long strands, 13 of which come together to form the microtubular structure.
• Microtubules act as a railway system for intracellular transport, by providing a surface to which motor proteins (dynein and kinesin) can attach.
• Microtubules are important for cell division - microtubules attach to kinetochores at the centromere of chromosomes, and as they break down they pull the chromosomes apart to separate sister chromatids.
• Microtubules form the base of cilia and flagella.
• Cilia helps to clear mucus in the respiratory tract and helps to move oocytes in the fallopian tubes.
• Flagella are important for the movement of sperm.
• Microtubules are ATP-dependent, meaning they require energy to move.