Membranous Organelles

Correct Combination of Organelles and Membrane Types

  • Question: Which of these options, row 1, 2, 3, or 4 describes a correct combination of organelles and their type of membrane in a human cell?

  • Options:

  1. Ribosome, Lysosome

    • Non-membrane bound, Single membrane-bound, Double membrane-bound

    • Peroxisome, Golgi body

    • Mitochondria, Nucleus

  2. Ribosome, Nucleolus

    • Golgi body, Cilia

    • Mitochondria, Mesosomes

  3. Cytoskeleton, Proteasome, Ribosome, Centriole

    • Lysosome, Vacuole

    • Mitochondria, Nucleus

  4. Centriole, Ribosome

    • Peroxisome, Golgi body

    • Mitochondria, Lysosome

Rough Endoplasmic Reticulum (RER)

  • Definition:

    • The Rough Endoplasmic Reticulum is a network of membranes known as "rough" due to ribosomes on its outer surface.

  • Functions:

    • Protein synthesis

    • Acts as a quality-control organelle for protein homeostasis (proteostasis).

      • Involved in quality control systems such as:

        • ER-associated degradation (ERAD)

        • Protein chaperones

        • Autophagy

        • Unfolded protein response (UPR) - This response occurs when ER stress is activated due to the accumulation of misfolded/unfolded proteins in the ER.

  • Structure:

    • Made up of membrane-bounded sacs, or cavities, coated with ribosomes. The interior is called the cisterna or lumen.

    • Continuous with the outer nuclear membrane, forming perinuclear cisterna and RER cisternae.

    • RER membranes possess receptors known as ribophorins that bind large ribosomal subunits.

Functions of RER

  • Protein Synthesis:

    1. Translation Steps:

      1. Signal recognition particle (SRP) binds to an initial signal peptide from the ribosome.

      2. SRP guides the ribosome to the RER receptor, which includes a pore-forming protein.

      3. The ribosome resumes translation, feeding polypeptides through the pore.

      4. Signal peptidase snips off the initial signal peptide.

      5. The completed polypeptide is released into the RER lumen.

  • Clinical Correlates:

    • ER dysfunction is linked to neurodegenerative diseases, including Alzheimer's, Parkinson’s, amyotrophic lateral sclerosis (ALS), and Huntington’s disease due to accumulation of misfolded proteins.

Smooth Endoplasmic Reticulum (SER)

  • Definition:

    • The smooth endoplasmic reticulum is a network of membranes without ribosomes on its surface, giving it a smooth appearance.

  • Functions:

    1. Prominent in steroid synthesis (e.g., Leydig cells).

    2. Facilitates fatty acid and phospholipid synthesis.

    3. Involved in drug detoxification within hepatocytes.

    4. Calcium ion storage and regulation, particularly in muscle contraction (involves the sarcoplasmic reticulum).

Clinical conditions associated with SER dysfunction:

  • Hypercholesterolemia

  • Reye's syndrome

  • Non-alcoholic fatty liver disease

Golgi Apparatus

  • Definition:

    • A stacked arrangement of membrane-bound cisternae involved in processing and sorting proteins synthesized in the RER.

  • Structure:

    • Cisternae formation is characterized by a distinct entry (cis) and exit (trans) polarity, where vesicles from the RER fuse at the cis face and secretory granules exit at the trans face.

  • Functions:

    1. Modifies proteins synthesized in the RER.

    2. Sorts proteins for final destinations:

    • Lysosomal enzymes delivered to lysosomes.

    • Secretory proteins sent to granules or into the extracellular space.

    • Membrane proteins incorporated into the cell membrane.

Membrane Trafficking

  • Definition:

    • The process of transporting proteins, lipids, and other molecules within and outside the cell using membrane-bound vesicles.

  • Coated Vesicles:

    • Membrane-bound structures that transport cargo between cellular compartments (e.g., RER to Golgi) characterized by a cytoplasmic surface coat.

  • Types of Coated Vesicles:

    1. Clathrin-coated vesicles

    2. Coatomer-coated vesicles

    3. Caveolin-coated vesicles

    4. Retromer-coated vesicles

Clathrin-coated Vesicles (CCVs):

  • Feature adaptins and consist of a triskelion structure formed by three large and three small polypeptide chains.

  • Function: intracellular transport via receptor-mediated endocytosis and sorted pathways from the trans-Golgi network to lysosomes.

  • Clinical Relevance:

    • Disorders associated with clathrin dysfunction include Lowe syndrome and Dent's disease due to mutations in associated genes.

Vesicular Transport

  • Definition:

  • Involves configurational changes in the plasma membrane at localized sites involving the actin cytoskeleton, leading to vesicle formation or fusion.

  • Types of Endocytosis:

    1. Pinocytosis:

    • "Cell drinking," involving clathrin-independent endocytosis with the ingestion of fluid and small molecules.

    1. Phagocytosis:

    • "Cell eating," a receptor-mediated process for engulfing large particles.

  • Receptor-Mediated Endocytosis:

  • Involves cargo receptors that recognize specific molecules for uptake. The clathrin coat helps select cargo for transport into cells.

Lysosomes

  • Structure:

    • Dense, diverse shapes, identifiable by cytochemical staining for acid phosphatase.

    • Membrane proteins protect from degradation by acid hydrolases.

  • Function:

    • Degradation of various biomolecules through fusion with late endosomes.

Clinical Relevance:
Lysosomal Storage Diseases (LSDs) such as Tay-Sachs disease and Gaucher disease are linked to lysosomal enzyme deficiencies.

Peroxisomes

  • Functions:

    • Contain enzymes for detoxification and oxidation of long-chain fatty acids. They synthesize cholesterol and form H2O2, which is broken down by catalase.

Mitochondria

  • Primary Function:

    • Generate ATP and possess their own circular DNA and ribosomes.

  • Morphological states of mitochondria can reflect their metabolic activity.

Proteasomes

  • Role in Intracellular Digestion:

    • Responsible for degradation of cytosolic proteins outside of lysosomal pathways via ubiquitination.

Inclusions

  • Definition:

    • Non-living, metabolically inactive materials (e.g., glycogen, lipid droplets, pigments).

Clinical Relevance:

  • Glycogen storage diseases can arise from the inability to properly metabolize glycogen.

Clinical Correlates

  • Brain Dopamine-Serotonin Vesicular Transport Disease:

    • Results from defects in vesicular transport systems; symptoms include dystonia and parkinsonism.

  • Lysosomal Storage Diseases (LSDs):

    • Caused by lysosomal enzyme mutations, leading to the accumulation of undigested materials.

  • Mitochondrial Disorders:

    • Diverse symptoms can include muscle weakness, seizures, and metabolic issues.

Common Examples:

  • Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)

  • Leigh Syndrome and Kearns-Sayre Syndrome