SUMMARY

• 21.1 A Proton Gradient Powers the Synthesis of ATP

  The flow of electrons through Complexes I, III, and IV of the electron-transport chain leads to the transfer of protons from the matrix side to the cytoplasmic side of the inner mitochondrial membrane. A proton-motive force consisting of a pH gradient (matrix side basic) and a membrane potential (matrix side negative) is generated. The flow of protons back to the matrix side through ATP synthase drives ATP synthesis. The enzyme complex is a molecular motor made of two operational units: a rotating component and a stationary component. The rotation of the γ subunit induces structural changes in the β subunit that result in the synthesis and release of ATP from the enzyme. Proton influx provides the force for the rotation.

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  The flow of two electrons through NADH-Q oxidoreductase, Q-cytochrome c oxidoreductase, and cytochrome c oxidase generates a gradient sufficient to synthesize 1, 1, and 0.5 molecule of ATP, respectively. Hence, 2.5 molecules of ATP are formed per molecule of NADH oxidized in the mitochondrial matrix, whereas only 1.5 molecules of ATP are made per molecule of FADH₂ oxidized, because its electrons enter the chain at QH₂, after the first proton-pumping site.

• 21.2 Shuttles Allow Movement Across Mitochondrial Membranes

  Mitochondria employ a host of transporters, or carriers, to move molecules across the inner mitochondrial membrane. The electrons of cytoplasmic NADH are transferred into the mitochondria by the glycerol 3-phosphate shuttle to form FADH₂ from FAD or by the malate–aspartate shuttle to form mitochondrial NADH. The entry of ADP into the mitochondrial matrix is coupled to the exit of ATP by ATP-ADP translocase, a transporter driven by membrane potential.

• 21.3 Cellular Respiration Is Regulated by the Need for ATP

  About 30 molecules of ATP are generated when a molecule of glucose is completely oxidized to CO₂ and H₂O. Electron transport is normally tightly coupled to phosphorylation. NADH and FADH₂ are oxidized only if ADP is simultaneously phosphorylated to ATP, a form of regulation called acceptor or respiratory control. Proteins have been identified that uncouple electron transport and ATP synthesis for the generation of heat. Uncouplers such as 2,4-dinitrophenol also can disrupt this coupling; they dissipate the proton gradient by carrying protons across the inner mitochondrial membrane.