Mitochondrial Oxidative Phosphorilation and Genetics

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Mitochondrial Oxidative Phosphorilation and
Genetics

• Abigail Hardy

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The Mitochondria

• Thousands of mitochondria in high energy areas
• Contact sites facilitate the entry of protiens
  into matrix
• Produces 90 of the cellular ATP in eukaryotic
  cells

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Major Protien Complexes
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Oxidative Phosphorylation

• Complexes I to IV, in addition to other
  components, act together as an electron transport
  chain
• Protons in intermembrane space form an
  electrochemical gradient, which provides
  potential energy used by complex V for the
  phosphorylation of ADP to ATP.

• Membrane channel protien (ANT) transports ATP out
  and ADP into matrix
• 11 ratio of transfer
• Both ADP and ATP move freely through the outer
  membrane

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Mitochondrial DNA

• Mitochondria have their own genetic apparatus
• Circular (16,568 bp)
• 2-10 separate mitochondrial gemomes in matrix
• Carries information for
• 2 rRNAs
• 22 tRNAs
• 13 proteins

• The 13 proteins encoded are involved in OXPHOS
  functions
• Nuclear genes encode about 70 additional protiens
  that make up the OXPHOS system
• A mitochondrion is the joint product of two
  different genetic systems

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Human Mitochondrial Genome
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Mitochondrial Replication

• During mitochondrial multiplication each genome
  is randomly distributed to a daughter
  mitochondrion
• Does NOT follow the Mendelian pattern of
  inheritance b/c not part of chromosomal system
• Details of mitochondrial reproduction are not
  known

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Mitochondrial Genetics

• Mitochondria of the zygote come from the oocyte
  (mother) and almost never the sperm (father)

• If the same set of symptoms in a number of
  various multigenerational families is inherited
  only from affected females and almost never from
  affected males, then there is a strong likelihood
  that it is caused by a mutation in one of the
  mitochondrial DNA genes

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Oocyte Mitochondria

• Human oocyte loses mitochondria as it matures
  through the genetic bottleneck
• Mitochondria are randomly distributed into
  daughter cells
• Mitochondrial Mutation Load the ratio of mutated
  to normal mitochondrial DNA

• Homoplasmy all mitochondria of a cell or tissue
  have the same genome
• Heteroplasmy contains both mutant and wild-type
  genomes
• Proportion of mutant to wild-type M. DNA
  determines if energy shortage occurs
• Threshold for phenotypic expression

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Bibliography

• Widmaier, E.P., Raff, H., Strang, K.T. Vanders
  Human Physiology The Mechanisms of Body
  Function. 10th ed. Boston McGraw-Hill, 2005.
• www.cbs.dtu.dk/staff/ dave/roanoke/bio101ch06.htm