Since it was first realized that biological energy transduction involves oxygen and ATP, opinions about the amount of ATP made per oxygen consumed have continually evolved. The coupling efficiency is crucial because it constrains mechanistic models of the electron-transport chain and ATP synthase, and underpins the physiology and ecology of how organisms prosper in a thermodynamically hostile environment. Mechanistically, we have a good model of proton pumping by complex III of the electron-transport chain and a reasonable understanding of complex IV and the ATP synthase, but remain ignorant about complex I. Energy transduction is plastic: coupling efficiency can vary. Whether this occurs physiologically by molecular slipping in the proton pumps remains controversial. However, the membrane clearly leaks protons, decreasing the energy funnelled into ATP synthesis. Up to 20% of the basal metabolic rate may be used to drive this basal leak. In addition, UCP1 (uncoupling protein 1) is used in specialized tissues to uncouple oxidative phosphorylation, causing adaptive thermogenesis. Other UCPs can also uncouple, but are tightly regulated; they may function to decrease coupling efficiency and so attenuate mitochondrial radical production. UCPs may also integrate inputs from different fuels in pancreatic β-cells and modulate insulin secretion. They are exciting potential targets for treatment of obesity, cachexia, aging and diabetes.
- oxidative phosphorylation
- P/O ratio
- proton leak
- uncoupling protein (UCP)
Abbreviations: ANT, adenine nucleotide translocase; H+/O ratio, H+/2e ratio, H+/ATP ratio, number of protons translocated across the mitochondrial inner membrane for each oxygen atom reduced to water, pair of electrons transferred from donor to acceptor, or ATP synthesized; P/O ratio, number of ATP molecules made by mitochondria from ADP for each oxygen atom consumed during substrate oxidation and oxidative phosphorylation; ROS, reactive oxygen species; UCP, uncoupling protein
- © 2005 The Biochemical Society