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.     

The uptake of inorganic carbon by freshwater plants

Abstract. The uptake of bicarbonate for photosynthetic assimilation by charophyte plants uses a chemiosmotic mechanism involving primary outward active transport of H⁺ in 'acid zones' of the membrane, and passive H⁺ re-entry in spatially separate 'alkaline' zones. In the process large electric currents circulate in the medium, and large local pH changes occur; bicarbonate ions, diffusing inwards across the unstirred layer of medium, encounter a number of competing mechanisms for the transfer of the carbon across the membrane. These are:

• i.

  transport of H₂CO₃ by diffusion
• ii.

  transport of CO₂ by diffusion; or
• iii.

  co-transport of HCO₃ and H⁺.

The decision amongst these mechanisms is not yet possible. There are parallels between the charophytes and aquatic angiosperms that are indicated, and contrasts with the chlorophytes.     

An in situ study of bioenergetic properties of human colorectal cancer: The regulation of mitochondrial respiration and distribution of flux control among the components of ATP synthasome

The aim of this study is to characterize the function of mitochondria and main energy fluxes in human colorectal cancer (HCC) cells. We have performed quantitative analysis of cellular respiration in post-operative tissue samples collected from 42 cancer patients. Permeabilized tumor tissue in combination with high resolution respirometry was used.Our results indicate that HCC is not a pure glycolytic tumor and the oxidative phosphorylation (OXPHOS) system may be the main provider of ATP in these tumor cells. The apparent Michaelis–Menten constant (K_m) for ADP and maximal respiratory rate (V_m) values were calculated for the characterization of the affinity of mitochondria for exogenous ADP: normal colon tissue displayed low affinity (K_m = 260 ± 55 μM) whereas the affinity of tumor mitochondria was significantly higher (K_m = 126 ± 17 μM). But concurrently the V_m value of the tumor samples was 60–80% higher than that in control tissue. The reason for this change is related to the increased number of mitochondria. Our data suggest that in both HCC and normal intestinal cells tubulin β-II isoform probably does not play a role in the regulation of permeability of the MOM for adenine nucleotides.The mitochondrial creatine kinase energy transfer system is not functional in HCC and our experiments showed that adenylate kinase reactions could play an important role in the maintenance of energy homeostasis in colorectal carcinomas instead of creatine kinase.Immunofluorescent studies showed that hexokinase 2 (HK-2) was associated with mitochondria in HCC cells, but during carcinogenesis the total activity of HK did not change. Furthermore, only minor alterations in the expression of HK-1 and HK-2 isoforms have been observed.Metabolic Control analysis showed that the distribution of the control over electron transport chain and ATP synthasome complexes seemed to be similar in both tumor and control tissues. High flux control coefficients point to the possibility that the mitochondrial respiratory chain is reorganized in some way or assembled into large supercomplexes in both tissues.