Presentation Speech by Professor Lars Ernster of the Royal Academy of Sciences
Translation from the Swedish text
Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,
The discoveries for which Peter Mitchell has been awarded this year’s Nobel Prize for Chemistry relate to a field of biochemistry often referred to in recent years as bioenergetics, which is the study of those chemical processes responsible for supplying energy to living cells.
All living organisms need energy to survive. Muscular work, thought processes, growth, and reproduction are all examples of biological activities that require energy. We know today that every living cell is capable, by means of suitable catalysts, of deriving energy from its environment, converting this energy into a biologically useful chemical form, and utilizing it for various energy-requiring processes.
Green plants and other photosynthetic organisms derive energy directly from sunlight – the ultimate source of energy for all life on Earth – and utilize this energy to convert carbon dioxide and water into organic compounds. Other organisms, including all animals and many bacteria, are dependent for their existence on organic compounds which they take up as nutrients from their environment. Through a process called cell respiration these compounds are oxidized by atmospheric oxygen to carbon dioxide and water with a concomitant release of energy.
Both respiration and photosynthesis involve a series of oxidation-reduction (or electron-transport) reactions in which energy is liberated and utilized for the synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate. These processes are usually called oxidative and photosynthetic phosphorylation. Both processes are typically associated with cellular membranes. In higher cells, they take place in special, membrane-enclosed organelles, called mitochondria and chloroplasts, while, in bacteria, both processes are associated with the cell membrane.
ATP serves as a universal energy currency for living cells. This compound is split by a variety of specific enzymes and the energy released is used for various energy-requiring processes. The regeneration of ATP by way of oxidative and photosynthetic phosphorylation thus plays a fundamental role in the energy supply of living cells.
The above concepts had been broadly outlined by about the middle of the 1950’s, but the exact mechanisms by which electron transport is coupled to ATP synthesis in oxidative and photosynthetic phosphorylation remained unknown. Many hypotheses were formulated, most of which postulated the ocurrence of ‘energy-rich’ chemical compounds of more or less well-defined structures as intermediates between the electron-transport and ATP-synthesizing systems. Despite intensive efforts in many laboratories, however, no experimental evidence could be obtained for these hypotheses. In addition, these hypotheses did not provide a rational explanation for the need for a membrane in oxidative and photosynthetic phosphorylation.
At this stage, in 1961, Peter Mitchell put forward his chemiosmotic hypothesis. The basic idea of this hypothesis is that the enzymes of the electron-transport and ATP-synthesizing systems are localized in the membrane with a well-defined orientation and are functionally linked to a vectorial transfer of positively charged hydrogen ions, or protons, across the membrane. Thus, electron transport will give rise to an electrochemical proton gradient across the membrane which can serve as a driving force for ATP synthesis. A requisite for the establishment of a proton gradient is, of course, that the membrane itself is impermeable to protons, which explains the need for an intact membrane structure in oxidative and photosynthetic phosphorylation.
The chemiosmotic hypothesis was received with reservation by many workers in the field which is, in a way, understandable, since it was unorthodox, fairly provocative, and based on little experimental evidence. Perhaps due to just these features, however, the hypothesis stimulated a great deal of activity; and it can be stated without exaggeration that during the last decade the chemiosmotic hypothesis has been the dominating issue in the field of bioenergetics both in the literature, at scientific meetings and, not least, in laboratories all over the world. As a result, a great deal of experimental data has been accumulated, both from Mitchell’s own laboratory – there mostly in collaboration with Dr. Jennifer Moyle – and from other places, which strongly supports the hypothesis. In fact, the basic postulates of the chemiosmotic hypothesis are today generally regarded as experimentally proven, thus making it a fundamental theory of cellular bioenergetics.
To understand the detailed mechanisms by which protons interact with and are translocated by the electron-transport and ATP-synthesizing systems will require further work. It is already clear, on the other hand, that the principle of power transmission by protonmotive force – or, as Mitchell has recently begun to call it, “proticity” (in analogy with electricity) – will be applicable to a wide range of biological processes beyond those involved in oxidative and photosynthetic phosphorylation. Uptake of neutrients by bacterial cells, intracellular transport of ions and metabolites, generation of reducing power for biosyntheses, biological heat production, bacterial motion and chemotaxis are examples of energy-requiring biological processes already known to be driven by proticity.
Finally, a practical aspect should be mentioned. The discovery that membrane-bound energy-transducing enzymes are so constructed that they can generate an electrochemical potential may be of great practical interest. Chloroplasts, mitochondria and bacteria may be regarded as naturally occurring solar cells and fuel cells, and may as such serve as models, and in the future perhaps also as tools, in energy technology. Obviously, once again, Nature has preceded man in inventiveness and may help him with her millions of years of experience in his daily struggle for life.
With ingenuity, courage and persistence you have innovated one of the classical fields of biochemistry. Your chemiosmotic theory has meant a breakthrough that has opened up new insights into the fundamental problems of bioenergetics. The details may need completion and adjustment; but the edifice you have raised will stand.
It is my great pleasure and privilege to convey to you the congratulations of the Royal Swedish Academy of Sciences on your outstanding achievements and to ask you to receive the Nobel Prize for Chemistry of 1978 from the hands of His Majesty the King.