An Issue of Originality and Priority: The Correspondence and Theories of Oxidative Phosphorylation of Peter Mitchell and Robert J.P. Williams, 1961–1980

In the same year, 1961, Peter D. Mitchell and Robert R.J.P. Williams both put forward hypotheses for the mechanism of oxidative phosphorylation in mitochondria and photophosphorylation in chloroplasts. Mitchell’s proposal was ultimately adopted and became known as the chemiosmotic theory. Both hypotheses were based on protons and differed markedly from the then prevailing chemical theory originally proposed by E.C. (Bill) Slater in 1953, which by 1961 was failing to account for a number of experimental observations. Immediately following the publication of Williams’s hypothesis and before his own was published, Mitchell initiated a correspondence. Examination of the letters shows the development of a dispute based on the validity of the proposals, who should have priority and particularly whether Mitchell had drawn on Williams’s work without acknowledgement. We have concluded that Mitchell’s proposals were original (a view still questioned by Williams) although it is evident that prior to the correspondence Williams had considered and rejected a proposition similar to Mitchell’s theory. However, a major cause of the dispute was the difference in disciplinary backgrounds of Mitchell, a microbial biochemist and Williams, a chemist.     

Glynn and the conceptual development of the chemiosmotic theory: A retrospective and prospective view

The origin and evolution of the chemiosmotic theory is described particularly in relation to Peter Mitchell's application of it to model oxidative phosphorylation. Much of the deployment, development and evaluation of the theory occurred at the independent laboratory of the Glynn Research Foundation; the value and future of such an institution is discussed. The role of models mediating between theories and phenomena is analyzed with regard to the growth of knowledge of chemiosmotic systems.     

Importance of mitochondrial transmembrane processes in human mitochondriopathies

In a substantial group of subjects suspected to have a mitochondriopathy no defect in the mitochondrial energy metabolism (pyruvate dehydrogenase complex or respiratory chain complexes) can be demonstrated. At least in some of these subjects it seems justified to consider a defect in one of the proteins which mediate the transport of several ions and substrates across the mitochondrial membranes. Of particular interest are proteins which are directly involved in the process of oxidative phosphorylation, such as the adenine nucleotide translocator (ANT) and the phosphate carrier (PiC). However, defects in transmembrane ion transporters also may induce impaired energy metabolism probably as a result of osmotic disturbances within the mitochondrial matrix. In this respect, the voltage-dependent anion channel (VDAC) and other ion channels have to be taken into consideration. Here we review the still incomplete knowledge of the occurrence of ANT, PiC, VDAC, cation channels, and a few substrate carriers in human tissues, as well as their possible role in pathology.