OXPHOS

Oxidative phosphorylation (OXPHOS) refers to the cellular process by which energy stored in reduced cofactors NADH and FADH2 is converted to ATP via the mitochondrial electron transport chain (ETC) and the enzyme ATP synthase. In eukaryotic cells, OXPHOS occurs in the inner mitochondrial membrane. NADH and FADH2, produced by glycolysis, the pyruvate dehydrogenase reaction, the citric acid cycle, and fatty acid beta-oxidation, donate electrons to the ETC. The electron transfer creates a proton gradient across the membrane by pumping protons from the matrix to the intermembrane space. The resulting electrochemical gradient, or proton motive force, powers ATP synthase (complex V), which synthesizes ATP from ADP and inorganic phosphate as protons flow back into the matrix.

Oxygen acts as the final electron acceptor at complex IV, forming water. OXPHOS is tightly coupled to respiration; uncoupling proteins or chemical uncouplers can dissipate the gradient, reducing ATP yield and increasing heat production. The efficiency is influenced by membrane integrity, substrate supply, and regulatory signals.

Common inhibitors include rotenone (complex I), antimycin A (complex III), cyanide and carbon monoxide (complex IV). Defects in OXPHOS underlie many mitochondrial diseases and age-related declines in energy metabolism. Clinical assessment often uses measurements of oxygen consumption rate and ATP production.