Histology: The Cell

• Mitochondria

  • unique and highly dynamic organelles
  • evolved as intracellular symbiont (endosymbiosis)
  • double membrane resembles a prokaryotic structure
  • has mtDNA (a circular genome with mitochondria-specific genes and proteins)
  • increase their numbers (overall biomass) via fission and fusion, do not rely (completely) on nuclear controls
• The purpose of the mitochondria is aerobic metabolism

  • the electron transport chain is embedded in the inner mitochondrial membrane (IMM)
  • the number of ETCs is limited by the surface area of the IMM
  • the need for more IMM surface area is the reason why the IMM is convoluted, forming cristae
• Mitochondria mediate cell death

  • apoptosis (specifically intrinsic apoptosis) is a form of programmed cell death and is often called “cell suicide“
  • damage to the cell is sensed by apoptotic proteins which permeabilize the OMM
  • cytochromeC release from the mitochondria intermembrane space is “the point of no return” for cells undergoing apoptosis
  • cytochromeC release initiates a cascade of subcellular events that results in pyknosis and eventually DNA fragmentation and cell death
• Microtubules

  • component of the cytoskeleton
  • regular, non-branching polymers of tubulin
  • hollow tubes
  • highly dynamic (can be polymerized and depolymerized rapidly)
  • grow from the microtubule organizing center (MTOC)
• Microtubules structure

  • structure of microtubules results in a polarity of the molecule
  • “+” end is B tubulin
  • “-“ end is a tubulin
  • microtubule grows only from the + end
  • the - end is attached to the MTOC via y-tubulin ring
• Microtubules Polymerization is dependent on

  • temperature
  • presence of GTP and Mg2+
  • presence of microtubule associated proteins (MAPs)
• Microtubule function

  • serve as infrastructure motor proteins (dyneins and kinesin)
  • mitotic spindle
  • cell elongation and migration
  • movement of cilia and flagella
• Actin Filaments

  • polymerize to form actin chains, two chains wrap around each other forming an actin filament (microfilaments)— thinner and shorter and more flexible than Microtubules
  • when free, actin is called G-actin (globular)
  • when polymerized, actin is called F-actin (filamentous)
  • f-actin has a fast growing end (plus, barbed) and a slow growing end (minus, pointy)
  • ATP, Mg2+, and K+ must be present for actin polymerization
  • ABP (actin binding proteins) can influence the structure and function of actin filament
• Actin filament functions

  • anchorage and movement of membrane protein
  • comprise the core of microvilli (a cell modification of absorptive cells, especially intestinal cells)
  • locomotion of cells and migration via lamellipodia (formed when cells crawl)
  • extension of filopodia
• Actin filaments — Stress fibers

  • stress fibers are higher order actin structures
  • stress fibers are contractile structures that consist of 10-30 actin filaments (found in non-muscle cells)
  • appear frequently in cultured cells (cancer cells and endothelial cells)
• Intermediate filaments

  • heterogenous group of similarly sized filaments
  • subunits are diverse but size remains constant
  • intermediate in size compared to actin filaments and microtubules
  • mostly for structure and anchoring
• Inclusions

  • structures of varying composition that have characteristics staining properties, typically cytoplasmic but may be nuclear
  • some of membranous (pigment granules) some are non-membranous (protein and glycogen aggregates)
• Inclusions — Lipofuscin

  • a “wear and tear” pigment that accumulates with age and oxidative stress
  • sign of cellular senescence (aging)
  • most apparent in long lived, non-dividing cells (neurons and cardiac muscle)
• Inclusions — glycogen

  • found in liver cells
  • seen when slides are stained in PAS or toluidine blue
• Inclusions — lipid

  • nutritive inclusions (energy storage)
  • lipid droplets have a membrane, but not a true bilayer
  • notoriously understudied
  • may be in cell for short time or for long-term storage
• Cytoplasmic matrix is a gel-like substance that holds the cell together and provides a place for chemical reactions to take place
• Nucleus

  • membranous organelles which contains the genome
  • cells are either currently dividing (M phase) or not dividing (G0) or preparing to divide (interphase)
  • G0 and interphase cells will appear similarly to us in the light microscope because the chromosomes are not compacted
  • nucleus contains chromatin (DNA + associated proteins — histones)
• Nucleoli

  • areas within the nucleus that RNA genes, rRNA, and proteins are present, areas of rRNA synthesis
• Chromatin

  • DNA and proteins together comprise chromatin
  • DNA + histones form a nucleoprotein complex
  • The nuclear material stains with basic dyes (basophilic) due to high DNA content
  • proteins allow for compact packaging of the genetic material into the small space of the nucleus
  • 2 formations: euchromatin = more relaxed in structure (light, less electron dense) and heterochromatin = highly condensed (dark, electron dense)
• Chromatin cells

  • metabolically active cells with have more euchromatin and often multiple nucleoli
  • inactive cells will have more heterochromatin and will often be smaller in size
  • appearance of nuclei can be informative — karyolysis (disappearance of nuclei due to DNAase activity), pyknosis (shrinking and condensation of the nuclei, preceded apoptosis), karyorrhexis (fragmentation of nuclei, after pyknosis, before phagocytes take cell carcasses up
• Nuclear envelope layers

  • semi-permeable barrier that contains the chromatin
  • outer nuclear membrane (continuous with the rER, may have ribosomes on it)
  • inner nuclear membrane (supported by intermediate filaments which attach to its inner surface called the nuclear lamina)
  • Perinuclear cisternal space (space between the two membranes that comprise the nuclear envelope)
• Nuclear envelope

  • lamina filaments are called “nuclear lamins” = intermediate filaments that are specific to the nucleus
  • Nuclear lamina maintain the shape of the nucleus and serve as scaffolding for the chromatin
  • Genetic diseases are associated with mutations in lamins (laminopathies) = include increased apoptosis and premature aging
• nuclear envelope structure

  • perforated by pores that extend through both membranes, named nuclear pores
  • formed by merging (fusion) of the inner and outer nuclear membranes at adjacent points
  • nuclear pores mediate active transport of proteins and RNA between the nucleus and cytoplasm
• Nuclear pore complex (structure)controls nuclear traffic and contain:

  • Cytoplasmic ring
  • nuclear ring
  • central plug/transporter
  • nuclear basket
  • terminal ring
  • central pore
• Getting proteins in/out of the nucleus

  • large molecules must enter and exit via the nuclear pore complex
  • newly synthesized proteins are destined for the nucleus contain a nuclear import signal (binds a nuclear receptor and then the protein is directed towards an appropriate nuclear pore complex to travel through)
  • proteins that must exit (riboproteins) contain a nuclear export signal
  • both signals are energy dependent
• Cell Renewal — at the tissue level

  • static cell populations — consist of cells that no longer divide (CNS, cardiac, muscle)
  • stable cell populations — consists of cells that maintain a population by proliferating episodically and slowly (smooth muscle, endothelium, fibroblasts)