MITOCHONDRIAL TRANSPORT SYSTEMS PROF' V' PELOUCH

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MITOCHONDRIAL TRANSPORT
SYSTEMSPROF. V. PELOUCH
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TRANSPORT MECHANISMS IN MITOCHONDRIA

• mitochondrion is divided into 4 compartments

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Different pathways localized in
mitochondria

• O u t e r m e m b r a n e
• Border against cytosol
• Relatively permeable even for big molecules

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CHARACTERISTICS OF BOTH M E M B R A N E S

• FEATURE INNER OUTER
• Thickness 5 -7 5 -7
  nm
• Shape folded
  smooth
• Surface outer part inner
  surface
• smooth
  smooth
• inner part
  outer surface
• regular units
  irregular
• Phospolipids remains intact - is
  abolished
• extraction

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CHARACTERISTICS OF BOTH M E M B R A N E S

• FEATURE INNER
  OUTER
• Permeability selective
  larger molecules pass freely
• Phospholipids/
• proteins ratio 0,27
  0,82
• Cardiolipin cont. high
  low
• PI content low
  high
• Cholesterol low
  high
• Coenzym Q present
  absent
• Monoamine oxidase absent
  present
• Cytochrom oxidase present
  absent

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Different pathways localized in
mitochondria

• I N N E R membrane
• Space composed of many enzymes and transporters
  (80 by proteins)
• Enzymes complex of oxidative phoshorylation
• Transporters malate
  lt--------------gt citrate
• malate
  lt--------------gt alpha-ketoglutarate
• pyruvate
  lt--------------gt OH-
• OH-
  lt--------------gt Pi
• Pi
  lt--------------gt malate
• ATP
  lt--------------gt ADP
• GLU
  lt--------------gt ASP
• ornithin,
  citrulin
• Shuttles malate aspartate (in muscles
  predominantly)
• glycerophoshate shunt (in
  liver)
• Carnitin transport system for FFA (acylCoA,
  carnitintransferase)

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TRANSPORT SYSTEMS

• Transport systems in the inner membrane
• simport (phosphate transporter)
• antiport (adenine nucleotide transporter)
• uniport (calcium transporter)
• Metabolic pathways
• Different pathways are localized in
  mitochondrial compartments

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TRANSPORT SYSTEMS
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DIFFERENT PATHWAYS LOCALIZED IN MITOCHONDRIA

• I N T E R M E M B R A N E space
• Space - where protons are pumped in
• pH is here, therefore, lower
• enzymes for exchange of different nucleotides
• 2 ADP lt---------gt ATP AMP)
• ADP is pumped into the matrix where is
• phoshorylated

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DIFFERENT PATHWAYS LOCALIZED IN MITOCHONDRIA

• M A T R I X of mitochondria
• Krebs cycle - substrates NADH and FADH are
  produced
• for oxidative phosphorylation
• Urea cycle - formation of urea from NH3 and
  CO2
• Synthesis of porphyrins and Hb GLY ALA
  succinyl CoA
• - metabolic pathways start in matrix and
  continues in cytosol

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DIFFERENT PATHWAYS LOCALIZED IN MITOCHONDRIA

• M A T R I X of mitochondria
• Transfer of different substrates on CoA
  metabolism of both sugars and lipids formation
  of acetylCoA - enters the Krebs cycle
• Degradation of FFA formation of acetylCoA -
  enters the Krebs cycle,
• furthermore, NADH and FADH enter the
  oxidative phosphorylation

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DIFFERENT PATHWAYS LOCALIZED IN MITOCHONDRIA
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DIFFERENT PATHWAYS LOCALIZED IN MITOCHONDRIA
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MITOCHONDRIAL SHUTTLES

• SHUTTLES
• Krebs cycle, degradation of FFA and oxidation of
  NADHH
• are localised, predominantly, in mitochondria
  
• however
• Inner membrane is not permeable for this
  nucleotide
• (as well as for oxaloacetate)
• therefore
• malate - aspartate shuttle (and
  glycerophoshate shuttle) are
• suitable for transport of these nucleotides
  formed in
• cytosol (e.g. in
  glycolysis)

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MITOCHONDRIAL SHUTTLES
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MITOCHONDRIAL SHUTTLES
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MECHANISMS OF PROTEINIMPORT INTO MITOCHONDRIA

• Apart from handful of proteins encoded by
  mitochondrial genome, most proteins localised
  in this organele are nuclear- encoded
  synthesised in the cytosol
• Translocation complexes of mitochondria
• a) TOM - translocases on outer
  membrane
• b) TIM - translocases on inner
  membrane
• c) Exporter - translocase on inner
  membrane
• 
  for
• mitochondrially
  encoded proteins
• that are
  synthetised in matrix and for
• some imported
  proteins exported
• to the inner
  membrane

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MECHANISMS OF PROTEINIMPORT INTO MITOCHONDRIA

• Protein trafficking is a vital cellular process
  in which proteins are transported from the site
  of their synthesis to the sites where they
  function
• Most of 1000 mitochondrial proteins are
  synthesised in cytosol and transported into or
  across the mitochondrial membranes

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MECHANISMS OF PROTEINIMPORT INTO MITOCHONDRIA