how do cells generate enertgy

• How cells generate energy
• The stepwise digestion of food in cells efficiently captures the energy

  1. Energy stored in activated carrier molecules: ATP

  2. Energy is release as heat; none is stored

  3. Nearly half of the energy derived from food is converted and stored

  4. A car engine only converts no more than 20% of energy from fuel to its useful work
• High energy bonds in ATP


  Utilized by cells to store and release energy
• An average person at rest consumes and regenerates ATP at a rate of 1.5 kg per hour and as much as 10 times faster during strenuous activity
• General steps to produce ATP from food

  1. Glycolysis

  2. Converting pyruvate to acetyl-CoA

  3. The citric acid cycle

  
• Glycolysis, converting pyruvate to acetyl-CoA, the citric acid cycle produce 4ATP + 10NADH + 2FADH2 + 6CO2 from 1 Glucose
• Mitochondria converts energy stored in high energy electrons in NADH and FADH2 to ATP
• Total around 36 ATP produced, over 88% of the ATP
• Mitochondria


  • Matrix: enzymes that produce acetyl-CoA and mediate the citric acid cycle
  • Inner membrane: transmembrane proteins that are important for generating ATP
  • Outer membrane: large channel-forming proteins and is permeable to molecules less than 5KD
  • Intermembrane space: enzymes using ATP to phosphorylate other nucleotides and regulate apoptosis
  • Mitochondrial DNA: tRNA, rRNA, components of the ATP-generating machinery

  
• Mitochondria are located near sites of high ATP utilization
• How mitochondria generate energy

  1. Electron transport chain

  2. Energy in electrochemical proton gradient

  3. Energy stored in ATP
• Electron transport chain


  • Transfer of high-energy electrons through respiratory enzyme complexes in the inner mitochondrial membrane
  • Complex I
  • Complex III
  • Complex IV
  • Coenzyme Q
• ATP synthase


  Converts the energy of proton flowing down their electrochemical gradient to chemical-bond energy in ATP
• Function of mitochondria is highly related to aging
• Aging is generally accompanied by: a decline in activity of mitochondrial enzymes, a decrease in respiratory capacity per mitochondria, an increase in the production of reactive oxygen species (ROS, a byproduct of the normal metabolism of oxygen)
• POLGγ


  The sole mitochondrial DNA polymerase, D257A mutant version has normal polymerase function but impaired proofreading activity
• Wild type mice vs POLGg(D257A) mutant mice at ∼13 months of age

  • Wild type: normal
  • POLGg(D257A) mutant: hair loss, graying, kyphosis, reduced life span
• Exercise rescues aging in mtDNA mutant mice
• Mitochondria morphology


  • PolG-SED mice (no exercise): swollen, oversized cristae, fragmentation, vacuolization
  • PolG-END mice (with exercise): normal mitochondria morphology
• Mitochondrial disorders cannot be cured, and available treatments can only relieving symptoms
• Mitochondrial disease


  People having the same genetic mutation may have very different symptoms; People having similar symptoms may caused by different genetic mutation
• Mitochondria undergo fission and fusion
• Molecular machineries regulate mitochondria fission and fusion

  • Mitofusin mediates mitochondira fusion
  • DRP1 mediates mitochondira fission
• Upregulation of mitochondrial fragmentation may interrupt normal function of mitochondria and induce cancer cells to become excessive proliferation
• Human lung cancer cells

  • Shown abnormal Mitochondrial fragmentation
• Inhibiting mitochondrial fission suppresses tumor growth
• How ATP synthase generate ATP