- Introduction to Cell Biology: Cell Structure, Organization, and Function

Learning Outcomes

  • By the end of the lecture, students should be able to:

    1. Produce a detailed overview of different cell systems and the evolutionary relationships between domains.

    2. Identify and describe important organelles and molecules in the cell with focus on structure-function relationships.

    3. Define the role of important organelles and molecules in the cell.

    • Fundamental point: All living organisms are composed of cells, the basic unit of life.

    • Assess knowledge: Contrast the structural differences between prokaryotes and eukaryotes.

Phylogenetic Tree of Life

  • Comparative rRNA sequencing (pioneered by Carl Woese) has defined three distinct lineages of cells, referred to as domains:

    1. Bacteria (Prokaryotic): Lacks a nucleus; cell walls typically contain peptidoglycan.

    2. Archaea (Prokaryotic): Lacks a nucleus; cell walls lack peptidoglycan; possess unique membrane lipids with ether linkages.

    3. Eukarya (Eukaryotic): Contains a membrane-bound nucleus and organelles.

  • Important distinctions:

    • Archaea and Bacteria are NOT closely related despite both being prokaryotic.

    • Archaea are more closely related to Eukarya than to Bacteria due to similar transcription and translation machinery.

Comparison of Bacteria, Archaea, and Eukarya

  • Bacteria (Prokaryotes):

    • DNA in nucleoid region (no nucleus)

    • Small cell size (0.2 - 2 \mu m)

    • High surface area-to-volume ratio (SA:V) allows for rapid nutrient exchange

  • Archaea:

    • Similar small size, DNA in circular chromosomes

    • Unique membrane structure (isoprenoid chains)

    • Many are extremophiles

  • Eukarya (Eukaryotes):

    • Larger cell size (10 - 100 \mu m)

    • Nucleus present, membrane-bound organelles

    • DNA in multiple linear chromosomes

Cell Organization - Key Organelles

  • Plasma Membrane:

    • Selectively permeable barrier

    • Contains integral and peripheral proteins

    • Fluid Mosaic Model: proteins in phospholipid bilayer

    • Cholesterol maintains fluidity

    • Glycolipids and glycoproteins for cell-cell recognition

  • Nucleus:

    • Contains the genome; site of DNA replication and transcription

    • Contains the nucleolus, where ribosomal RNA (rRNA) is synthesized

    • Nuclear envelope has pores (100 nm diameter) regulating traffic

  • Ribosomes:

    • Translate mRNA into polypeptides

    • Eukaryotic (80S): 60S large subunit + 40S small subunit

    • Prokaryotic (70S): 50S + 30S subunits (antibiotic target)

  • Rough Endoplasmic Reticulum (RER):

    • Studded with ribosomes

    • Site of synthesis for membrane-bound and secreted proteins

    • Involved in N-linked glycosylation

    • Produces hydrogen peroxide (H_2O_2) as byproduct of oxidative protein folding

  • Smooth Endoplasmic Reticulum (SER):

    • Lacks ribosomes

    • Functions: lipid synthesis, steroid hormone production, carbohydrate metabolism

    • Sequestration of calcium ions (Ca^{2+})

    • Contains Cytochrome P450s (CYP450) for drug detoxification

  • Golgi Apparatus:

    • Modifies proteins (O-linked glycosylation) and sorts them

    • Cis face: receiving side (near ER)

    • Trans face: shipping side (gives rise to vesicles)

  • Lysosomes:

    • Acidic organelles (pH \approx 4.5 - 5.0)

    • Contain over 40 types of hydrolytic enzymes (acid hydrolases)

    • Degrade macromolecules and old organelles (autophagy)

  • Peroxisomes:

    • Break down fatty acids and detoxify harmful substances

    • Produce hydrogen peroxide (H_2O_2) as byproduct, converted to water by catalase

    • Enclosed in single membrane (different from lysosomes)

  • Mitochondria:

    • Site of cellular respiration and ATP generation

    • Double membrane: smooth outer membrane and folded inner membrane (cristae)

    • Contains its own circular DNA and ribosomes

    • NADH transfers electrons from TCA cycle to electron transport chain

  • Cytoskeleton:

    • Microtubules (25 nm): Composed of tubulin; provide tracks for motor proteins (kinesin/dynein)

    • Microfilaments (7 nm): Composed of actin; involved in muscle contraction and cell motility

    • Intermediate Filaments (8 - 12 nm): Provide mechanical strength (e.g., keratin); disassembly regulated by phosphorylation

Endomembrane System

  • Network includes: nuclear envelope, ER, Golgi, lysosomes, vesicles, and plasma membrane

  • Related through direct continuity or transfer of membrane segments as vesicles

  • Vesicular transport: docking ensured by SNARE proteins

Central Dogma

  • DNA → RNA → Protein

    • Transcription: In nucleus, DNA template creates pre-mRNA

    • RNA Processing: Splicing and capping before leaving nucleus

    • Translation: In cytoplasm (on ribosomes), mRNA determines amino acid sequence

  • Nuclear Localisation Signal (NLS) recognized by Importin

Cell Signaling

  • SH2 domain: enables binding to phosphotyrosine residues

  • Receptor tyrosine kinases activate Ras

  • EGFR signaling pathway targeted by drugs like Gefitinib

Degradative Pathways

  • Three pathways: Phagocytosis, Endocytosis, Autophagy

Apoptosis

  • Intrinsic pathway involves Cytochrome c

  • Pro-apoptotic protein: Bax

  • Tumor suppressor: p53