Mitochondria

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Mitochondria
Guest lecturer Chris Moyes, Dept of
Biology Contact moyesc_at_biology.queensu.ca
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Endosymbiosis
Mitochondria formed as a result of an
endosymbiotic event around 2 billion years ago.
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From Gerhart and Kirschner Cells, Embryos and
Evolution
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Mitochondrial compartments

• Inner membrane
• Respiratory chain and ATP synthase
• impermeable to most charged molecules
• highly folded into invaginations called cristae.
• Outer membrane
• Permeable to larger molecules
• Matrix
• Enzymes of the citric acid cycle, mtDNA
• Intermembrane space
• space between inner and outer membranes

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Mitochondrial compartments
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Mitochondrial morphology and movement

• Mitochondria are dynamic organelles
• they may exist as individual organelles
• may become elaborate network
• move throughout the cell on cytoskeleton
• Changes in the network are mediated by fission
  and fusion proteins

• Fuzzy Onion Protein (FZO) causes fusion

• Dynamin-Related Protein causes fission

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Mitochondrial reticulum
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Fusion and fission proteins regulate network
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Mitochondrial energy production
Three major steps in oxidative phosphorylation 1)
Production of reducing equivalents (NADH, FADH2)
from glycolysis, fatty acid oxidation, and the
citric acid cycle 2) Electron transport and
generation of proton motive force 3)
Phosphorylation - Synthesis of ATP, driven by the
proton motive force
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Mitochondria make other products

• Mitochondria produce biosynthetic precursors
• OXPHOS also leads to the production of
• Superoxide formed when O2 steals electrons from
  the ETC complexes
• Heat a by-product of the reactions of OXPHOS

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Overview of energy production by OXPHOS
Show 14-10, gen overview
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Reducing equivalents are produced in the
oxidation of carbohydrate and lipid
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Oxidation and Electron Transport
Electrons from NADH and FADH2 are passed down
respiratory chain to O2
Electron transport expels protons, creating a
proton gradient- the proton motive force (PMF)
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Proton motive force (PMF)
The PMF is an electrochemical gradient of
membrane potential (??) and pH (?pH)
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The PMF supplies the energy for active transport
into the mitochondria
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Phosphorylation
The F1Fo ATPase (or ATP synthase) is a molecular
motor -it uses the PMF to make ATP -it can also
be reversed (using ATP hydrolysis to recharge the
PMF)
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Oxidation and phosphorylation are coupled by a
shared dependence on the PMF
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Because of this coupling, the two processes are
interdependent

• If the PMF is large, what would you predict about
  oxygen consumption?
• If you took away oxygen, what would happen to the
  PMF?
• What would an increase in ADP do to the oxygen
  consumption?
• What would happen to ATP synthesis and oxygen
  consumption if the inner membrane became leaky?

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Uncoupling proteins
Many mammals warm vital tissues using brown fat
Adipose tissue with abundant mitochondria that
possess a the protein thermogenin (or uncoupling
protein 1). UCP-1 short-circuits the proton
gradient, increasing VO2 and heat
production. All eukaryotes have proteins related
to UCPs, that are thought to prevent the PMF from
over-charging, thereby reducing ROS production.
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Mitochondrial biogenesis requires proteins
encoded in 2 genomes (nucleus and mtDNA)
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Peculiarities of mtDNA

• mtDNA is a very compact genome
• -genes attached end to end, with mRNA regions
  interspersed among rRNA and tRNA genes
• -tRNA excision liberates protein-coding genes
• -many genes lack a full termination codon (TAA)
• Diversity
• -maternal origin (most animals)
• -many cells have multiple genotypes within a
  single cell (heteroplasmy)
• -defects accumulate with age

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Editing of mtDNA polycistron
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Nuclear gene expression is coordinated by
transcription factor networks
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Mt enzyme synthesis requires coordinated gene
expression and accessory factors