Oxidative Phosphorylation, Mitochondrial Function, and Oxygen Radicals

• The reduced cofactors generated during fuel oxidation donate their electrons to the mitochondrial electron transport chain.
• The electron transport chain transfers the electrons to O₂, which is reduced to water.
• As electrons travel through the electron transport chain, protons are transferred from the mitochondrial matrix to the cytosolic side of the inner mitochondrial membrane.
• The asymmetrical distribution of protons across the inner mitochondrial membrane generates an electrochemical gradient across the membrane.
  The electrochemical gradient consists of a change in pH (ΔpH) across the membrane, and a difference in charge (ΔΦ) across the membrane.
• Proton entry into the mitochondrial matrix is energetically favorable and drives the synthesis of ATP via the ATP synthase.
• Respiration (O₂ consumption) is normally coupled to ATP synthesis; if one process is inhibited, the other is also inhibited.
• Uncouplers allow respiration to continue in the absence of ATP synthesis, as the energy inherent in the proton gradient is released as heat.
• Through a number of enzymatic and nonenzymatic processes O₂ can accept a single electron to form reactive oxygen species.
• The major reactive oxygen species are the radicals superoxide and hydroxyl radical and the nonradical hydrogen peroxide.
• Reactive oxygen species cause damage to lipids, proteins, and DNA within cells.
• Cellular defense mechanisms exist to protect against inadvertent radical formation.