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After studying this chapter, you should be able to:


  • Describe the double membrane structure of mitochondria and indicate the location of various enzymes.
  • Appreciate that energy from the oxidation of fuel substrates (fats, carbohydrates, amino acids) is almost all liberated in mitochondria as reducing equivalents, which are passed by a process termed electron transport through a series of redox carriers or complexes embedded in the inner mitochondrial membrane known as the respiratory chain until they are finally reacted with oxygen to form water.
  • Describe the four protein complexes involved in the transfer of electrons through the respiratory chain and explain the roles of flavoproteins, iron sulfur proteins, and coenzyme Q.
  • Understand how coenzyme Q accepts electrons from NADH via Complex I and from FADH2 via Complex II.
  • Indicate how electrons are passed from reduced coenzyme Q to cytochrome c via Complex III in the Q cycle.
  • Explain the process by which reduced cytochrome c is oxidized and oxygen is reduced to water via Complex IV.
  • Understand how electron transport through the respiratory chain generates a proton gradient across the inner mitochondrial membrane, leading to the buildup of a proton motive force that generates ATP by the process of oxidative phosphorylation.
  • Describe the structure of the ATP synthase enzyme and explain how it works as a rotary motor to produce ATP from ADP and Pi.
  • Identify the five conditions controlling the rate of respiration in mitochondria and understand that oxidation of reducing equivalents via the respiratory chain and oxidative phosphorylation are tightly coupled in most circumstances, so that one cannot proceed unless the other is functioning.
  • Indicate examples of common poisons that block respiration or oxidative phosphorylation and identify their site of action.
  • Explain, with examples, how uncouplers may act as poisons by dissociating oxidation via the respiratory chain from oxidative phosphorylation, but may also have a physiological role in generating body heat.
  • Explain the role of exchange transporters present in the inner mitochondrial membrane in allowing ions and metabolites to pass through while preserving electrochemical and osmotic equilibrium.


Aerobic organisms are able to capture a far greater proportion of the available free energy of respiratory substrates than anaerobic organisms. Most of this takes place inside mitochondria, which have been termed the “powerhouses” of the cell. Respiration is coupled to the generation of the high-energy intermediate, ATP, by oxidative phosphorylation. A number of drugs (eg, amobarbital) and poisons (eg, cyanide, carbon monoxide) inhibit oxidative phosphorylation, usually with fatal consequences. Several inherited defects of mitochondria involving components of the respiratory chain and oxidative phosphorylation have been reported. Patients present with myopathy and encephalopathy and often have lactic acidosis.


Mitochondria have an outer membrane that is permeable to most metabolites and an inner membrane that is selectively permeable, enclosing a matrix within (Figure 13–1). The outer membrane is characterized by the presence of various enzymes, including acyl-CoA synthetase and glycerolphosphate acyltransferase.Adenylyl kinase and creatine...

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