Peter Mitchell

Bio: Peter Mitchell is an academic researcher from University of Edinburgh. The author has contributed to research in topics: Respiratory chain & Chemiosmosis. The author has an hindex of 47, co-authored 79 publications receiving 17001 citations.

Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic type of Mechanism

Abstract: Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic type of Mechanism

Chemiosmotic coupling in oxidative and photosynthetic phosphorylation

Abstract: 50 years ago Peter Mitchell proposed the chemiosmotic hypothesis for which he was awarded the Nobel Prize for Chemistry in 1978. His comprehensive review on chemiosmotic coupling known as the first "Grey Book", has been reprinted here with permission, to offer an electronic record and easy access to this important contribution to the biochemical literature. This remarkable account of Peter Mitchell's ideas originally published in 1966 is a landmark and must-read publication for any scientist in the field of bioenergetics. As far as was possible, the wording and format of the original publication have been retained. Some changes were required for consistency with BBA formats though these do not affect scientific meaning. A scanned version of the original publication is also provided as a downloadable file in Supplementary Information and can be found online at doi:10.1016/j.bbabio.2011.09.018. See also Editorial in this issue by Peter R. Rich. Original title: CHEMIOSMOTIC COUPLING IN OXIDATIVE AND PHOTOSYNTHETIC PHOSPHORYLATION, by Peter Mitchell, Glynn Research Laboratories, Bodmin, Cornwall, England.

Keilin's respiratory chain concept and its chemiosmotic consequences.

Abstract: It was obviously my hope that the chemiosmotic rationale of vectorial metabolism and biological energy transfer might one day come to be generally accepted, and I have done my best to argue in favour of that state of affairs for more than twenty years. But, it would have been much too presumptuous to have expected it to happen. Of course, I might have been wrong, and in any case, was it not the great Max Planck (1928, 1933) who remarked that a new scientific idea does not triumph by convincing its opponents, but rather because its opponents eventually die? The fact that what began as the chemiosmotic hypothesis has now been acclaimed as the chemiosmotic theory-at the physiological level, even if not at the biochemical level-has therefore aroused in me emotions of astonishment and delight in full and equal measure, which are all the more heartfelt because those who were formerly my most capable opponents are still in the prime of their scientific lives. I shall presently explain the difference between the physiological and the biochemical levels at which the chemiosmotic theory has helped to promote useful experimental research. But let me first say that my immediate and deepest impulse is to celebrate the fruition of the creative work and benevolent influence of the late David Keilin, one of the greatest of biochemists and-to me, at least-the kindest of men, whose marvellously simple studies of the cytochrome system, in animals, plants and microorganisms (Keilin, 1925), led to the original fundamental idea of aerobic energy metabolism: the concept of the respiratory chain (Keilin, 1929; and see Nicholls, 1963; King, 1966). Perhaps the most fruitful (and surprising) outcome of the development of the notion of chemiosmotic reactions is the experimental stimulus and guidance it has provided in work designed to answer the following three elementary questions about respiratory chain systems and analogous photoredox chain systems: What is it? What does it do? How does it do it? The genius of David Keilin led to the revelation of the importance of these questions. In this lecture, I hope to show that, as a result of the painstaking work of many biochemists, we can now answer the first two in general principle, and that considerable progress is being made in answering the third. Owing to the broad conceptual background, and the very wide range of practical application of the chemiosmotic theory, I have had …

Energy conservation in chemotrophic anaerobic bacteria.

Abstract: [This corrects the article on p. 100 in vol. 41.].

Mitochondrial Membrane Permeabilization in Cell Death

Abstract: Irrespective of the morphological features of end-stage cell death (that may be apoptotic, necrotic, autophagic, or mitotic), mitochondrial membrane permeabilization (MMP) is frequently the decisive event that delimits the frontier between survival and death. Thus mitochondrial membranes constitute the battleground on which opposing signals combat to seal the cell's fate. Local players that determine the propensity to MMP include the pro- and antiapoptotic members of the Bcl-2 family, proteins from the mitochondrialpermeability transition pore complex, as well as a plethora of interacting partners including mitochondrial lipids. Intermediate metabolites, redox processes, sphingolipids, ion gradients, transcription factors, as well as kinases and phosphatases link lethal and vital signals emanating from distinct subcellular compartments to mitochondria. Thus mitochondria integrate a variety of proapoptotic signals. Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria. These catabolic enzymes as well as the cessation of the bioenergetic and redox functions of mitochondria finally lead to cell death, meaning that mitochondria coordinate the late stage of cellular demise. Pathological cell death induced by ischemia/reperfusion, intoxication with xenobiotics, neurodegenerative diseases, or viral infection also relies on MMP as a critical event. The inhibition of MMP constitutes an important strategy for the pharmaceutical prevention of unwarranted cell death. Conversely, induction of MMP in tumor cells constitutes the goal of anticancer chemotherapy.

Chemiosmotic coupling in oxidative and photosynthetic phosphorylation

Abstract: 50 years ago Peter Mitchell proposed the chemiosmotic hypothesis for which he was awarded the Nobel Prize for Chemistry in 1978. His comprehensive review on chemiosmotic coupling known as the first "Grey Book", has been reprinted here with permission, to offer an electronic record and easy access to this important contribution to the biochemical literature. This remarkable account of Peter Mitchell's ideas originally published in 1966 is a landmark and must-read publication for any scientist in the field of bioenergetics. As far as was possible, the wording and format of the original publication have been retained. Some changes were required for consistency with BBA formats though these do not affect scientific meaning. A scanned version of the original publication is also provided as a downloadable file in Supplementary Information and can be found online at doi:10.1016/j.bbabio.2011.09.018. See also Editorial in this issue by Peter R. Rich. Original title: CHEMIOSMOTIC COUPLING IN OXIDATIVE AND PHOTOSYNTHETIC PHOSPHORYLATION, by Peter Mitchell, Glynn Research Laboratories, Bodmin, Cornwall, England.

Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

Abstract: Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo.