Key Concepts of Section 12.5

• Peter Mitchell proposed the chemiosmotic hypothesis that a proton-motive force across the inner mitochondrial membrane is the immediate source of energy for ATP synthesis.

• Bacteria, mitochondria, and chloroplasts all use the same chemiosmotic mechanism and a similar ATP synthase to generate ATP (see Figure 12-30).

• ATP synthase (also called the F₀F₁ complex) catalyzes ATP synthesis as protons flow through the inner mitochondrial membrane (the plasma membrane in bacteria) down their electrochemical proton gradient.

• F₀ contains a ring of 8–14 c subunits, depending on the organism, that is rigidly linked to the rod-shaped γ subunit and the ε subunit of F₁. These subunits rotate during ATP synthesis. Resting atop the γ subunit is the hexameric knob of F₁ [(αβ)₃], which protrudes into the mitochondrial matrix (cytosol in bacteria). The three β subunits are the sites of ATP synthesis (see Figure 12-31 and 12-34a and b).

• Rotation of the F₁ γ subunit, which is inserted in the center of the nonrotating (αβ)₃ hexamer and operates like a camshaft, leads to changes in the conformation of the nucleotide-binding sites in the three F₁ β subunits (see Figure 12-32). By means of this binding-change mechanism, the β subunits bind ADP and P_i, condense them to form ATP, and then release the ATP. Three ATPs are made for each revolution of the assembly of c, γ, and ε subunits.

• Movement of protons across the membrane via two half-channels at the interface of the F₀ a subunit and the c ring powers rotation of the c ring with its attached F₁ ε and γ subunits.

• The F₀F₁ complex bends the inner mitochondrial membrane, contributing to its characteristic high curvature and to the tubular and pancake-like structures of the cristae (see Figure 12-34c and d).

• The proton-motive force also powers the uptake of P_i and ADP from the cytosol in exchange for mitochondrial ATP and OH⁻, thus reducing the energy available for ATP synthesis. The ATP/ADP antiporter that participates in this exchange is one of the most abundant proteins in the inner mitochondrial membrane (see Figure 12-35).

• Continued mitochondrial oxidation of NADH and reduction of O₂ are dependent on sufficient ADP being present in the matrix. This phenomenon, termed respiratory control, is an important mechanism for coordinating oxidation and ATP synthesis in mitochondria.

• In brown fat, the inner mitochondrial membrane contains the uncoupler protein thermogenin, a proton transporter that dissipates the proton-motive force into heat. Certain chemicals also function as uncouplers (e.g., DNP) and have the same effect, uncoupling oxidative phosphorylation from electron transport. There are two distinct types of thermogenic fat cells: brown-fat and beige-fat cells.