Mitochondrial Structure & Function

Structure of the Mitochondrion

Mitochondria have their own genome & ability to manufacture own RNA and proteins

Their ribosomes = 70S type (30S & 50S) i.e same as bacteria (rest of cell has 80S ribosomes)

• 1-10µ
• Consist of two membranes (outer and inner)
  • Outer membrane
    • encloses whole organelle
    • contains several integral proteins = porins
    • porins form large aqueous channels which allow passage of movement of molecules up to 5000D (pyruvate, amino acids, fatty acids)
  • Intermembrane space
    • between outer & inner membrane
    • chemically equivalent to cells cytosol
    • contains cytochrome-c
  • Inner membrane:
    • No porins
    • controlled permeability via transporter proteins
    • Different functions
      • proteins carrying out oxidative reactions of resp chain
      • ATP synthase – makes ATP in matrix
      • Transport proteins
      • Protein import machinery
  • Cristae:
    • Formed by folded inner membrane
    • Vastly ↑s surface area for ATP production
    • Cells which more active e.g myocardium have more cristae
  • Inner mitochondrial matrix
    • Space enclosed by inner membrane
    • Impt in ATP production
    • Contains highly conc mixture of
      • hundreds of enzymes
      • mitochon ribosomes (70S)
      • tRNA
      • several copies of DNA genome
    • Contents important in many metabolic processes:
      • Citric acid cycle
      • Pyruvate metabolsim
      • Fatty acid metabolism
      • Urea cycle
    • Haeme synthesis
• There are several mitochondria are found within a cell – They replicate independently of the cell’s state of division (as they possess their own DNA), and they replicate in response to the metabolic demands of the cell (Ie. number of mitochondria reflects metabolic activity of the cell)
• Mitochondria DNA is unique from nuclear DNA in that it is:
  • Contains both double-stranded circular DNA and plasmid DNA, which are both maternally-inherited
  • only 1% of mitochondrial proteins (esp enzymes for oxidative phosphorylation) – Remaining 99% of proteins are encoded by nuclear DNA

Function of the Mitochondrion

• Form ATP via oxidative phosphorylation (Major), via Kreb’s cycle and Electron Transport Chain
• Regulation of Cellular proliferation regulation including cell division and differentiation (contributes ATP)
• Regulation of cellular metabolism
• Regulate apoptosis
• Xenobiotic metabolism (esp role of MAO)
• Heat production (esp in brown fat)
  • By proton leak or mitochondrial uncoupling
    • proton re-enters mitochondrial matrix without contributing to ATP synthesis → heat released
  • mediated by therminogenin (proton channel)
• Sequestration of Ca2+ ions (with swelling/damage post-ischaemia)
  • acts as cytosolic buffers for calcium
  • Significant interplay with Endoplasmic reticulum
  • primary driven by mitochondrial membrane potential
  • released back into cell’s interior via Na⁺-Ca²⁺ exchange protein or Calcium-induced-Calcium-release pathways
  • Calcium also necessary to activate isocitrate dehydrogenace (Kreb’s cycle)
• Signaling through mitochondrial reactive oxygen species
• Cholesterol and steroid synthesis
• Certain haeme synthesis reactions
• Organ specific functions:
  • Neuronal: contribute to cellular quality control by reporting neuronal status towards microglia through specialised somatic-junction
  • Liver: Detoxify ammonia

Oxidative Phosphorylation – Mitcochondria Energy Production

• mitochon found in high conc in cells with high metabolic demands eg myocardium (23% of cell), brown fat (neonate)
• exercise ↑s numbers
• OP = production of ATP associated with oxidation by the flavoprotein cytochrome system in mitochondria

• ATP formed in electron transfer chain:
  • Substrate diffuses into mitochon cytoplasm
  • Hydrogen removed by a dehydrogenase
  • NAD carries hydrogen to respiratory chain
  • Hydrogen ionises and protons pass along series of carrier molecules across insulating membrane (inner membrane of mitochondria – forms cristae)
  • Movement of protons creates an electrochemical gradient for transport of protons from intermediate space back into matrix ⇒ this drives a reversible ATPase in inner membrane (ATP synthase)
  • ATP synthase: ADP + Pi ⇒ ATP
  • @end:
    • ATP produced
    • Reduction of O2 to water – catalysed by cytochrome oxidase
      • cyanide inhibits this oxidase ∴ inhibits OP in mitochon
    • O2 required to oxidise NADH
• Eg’s of carrier molecules in electron transfer chain
  • Flavoprotein
  • Cytochromes A, A3, B, C, C1
  • Ubiquinone
  • Several iron sulphide proteins
• OP depends on:
  • Adequate supply of ADP: +ve feedback loop e.g. ↑ATP utilisation ⇒ ↑ADP ⇒ ↑OP
  • Rate of delivery of fats, lactate, glucose to interior of mitochon
  • Availability of O2: Pasteur point = 1-2mmHg i.e. point below which OP cannot occur
• ∴ cardioresp works in harmony to ensure o2 reaches cells
  • defined by oxygen flux equation:

• lack of oxygen causes:
  • nothing to scavenge H+ at end of transfer chain
  • transfer chain ceases
  • build up of reduced compounds ⇒ inhibits TCA cycle ⇒ inhibition of glycolysis
    • but glycolysis continues as lactate dehydrogenase removes reduced compounds

Side note: breakdown of 1 glucose molecule:

JC 2019

Answer by JC