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Peter D. Mitchell, who was awarded the Nobel Prize in Chemistry 30 years ago, in 1978, formulated the chemiosmotic theory of oxidative phosphorylation. This review initially analyzes the major aspects of this theory, its unresolved problems, and its modifications. A new physico-chemical mechanism of energy transformation and coupling of oxidation and phosphorylation is then suggested based on recent concepts regarding proteins, including ATPases that work as molecular motors, and acidic lipids that act as hydrogen ion (H(+)) carriers. According to this proposed mechanism, the chemical energy of a redox substrate is transformed into nonequilibrium states of electron-transporting chain (ETC) coupling proteins. This leads to nonequilibrium pumping of H(+) into the membrane. An acidic lipid, cardiolipin, binds with this H(+) and carries it to the ATP-synthase along the membrane surface. This transport generates gradients of surface tension or electric field along the membrane surface. Hydrodynamic effects on a nanolevel lead to rotation of ATP-synthase and finally to the release of ATP into aqueous solution. This model also explains the generation of a transmembrane protonmotive force that is used for regulation of transmembrane transport, but is not necessary for the coupling of electron transport and ATP synthesis.

Citation

Nikolai Kocherginsky. Acidic lipids, H(+)-ATPases, and mechanism of oxidative phosphorylation. Physico-chemical ideas 30 years after P. Mitchell's Nobel Prize award. Progress in biophysics and molecular biology. 2009 Jan;99(1):20-41

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PMID: 19049812

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