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BBA - Molecular Cell Research
Assembly of the Mitochondrial Respiratory Chain
Edited by Dennis Winge and Alexander Tzagoloff
Volume 1793, Issue 1, Pages 1-218 (January 2009)
Mitochondria gained recognition as important cellular organelles in the mid 1900’s when their function as the centers of respiration was first realized from a convergence of electron microscopic and biochemical evidence. In the following decades a great deal of attention was directed to deciphering the mechanism by which the energy released during the oxidation of NADH and succinate is conserved in the form of ATP. In a striking departure from the then prevailing dogma, Peter Mitchell formulated the chemiosmotic hypothesis, which proposed that the linear transfer of electrons through the respiratory chain complexes is coupled to a vectorial transfer of protons across the inner membrane, thereby generating an electrochemical potential capable of supporting ATP synthesis. Although slow to be accepted by the establishment of the day, the chemiosmotic mechanism has become one of the cornerstones of modern biology. The conundrum remained of how the ATP synthase uses the proton gradient to form ATP. This important problem was solved by Paul Boyer who proposed a conformational model for a direct phosphorylation of ADP, dispensing with the need to invoke the involvement of chemical intermediates that had not been detected despite concerted efforts on the part of many labs. It is unprecedented that evolution devised two entirely different solutions for a process as fundamental as conservation of energy.
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