Oxidative Phosphorylation
The metabolic pathway in mitochondria where ATP is generated using energy from electron transport chain reactions. Oxidative phosphorylation produces the majority of cellular ATP. Disruption of this process (as in Barth syndrome) leads to energy deficiency affecting high-demand organs like the heart and skeletal muscle.
Technical Context
Mitchell's chemiosmotic hypothesis (Nobel Prize 1978): ETC complexes pump protons from the matrix to the intermembrane space, creating an electrochemical gradient (~180mV membrane potential). ATP synthase harnesses this proton-motive force: protons flow through the Fo subunit (membrane-embedded rotor), driving rotation of the c-ring, which rotates the γ-subunit within the F1 catalytic head (containing three αβ catalytic sites), inducing conformational changes that catalyse ADP + Pi → ATP (binding change mechanism, Boyer — Nobel Prize 1997). Coupling efficiency: normally approximately 40% of the potential energy in the proton gradient is captured as ATP; the remainder is dissipated as heat (contributing to thermogenesis — important for temperature maintenance). Uncoupling proteins (UCP1 in brown adipose tissue) deliberately dissipate the proton gradient as heat (non-shivering thermogenesis). In Barth syndrome, disrupted cristae and supercomplex disassembly reduce coupling efficiency, compounding the ATP deficit with increased heat production and ROS generation.