Coupling in mitochondria

Gel immobilized cells Mammalian cells Glucose 0.980 1.05 Chresand et at (1988) 

Biofilm (natural) on E. coli Nitrous oxide 0.860 1.00 Libicki et at (1988) 

Gel immobilized cells S. cerevisiae Lactose 0.882 0.96 Axelsson and Persson (1988) 

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Carafoli E, Rossi CS, Lehninger AL. 1965. Energy-coupling in mitochondria during resting of state 4 respiration. Biochem Biophys Res Commun 19(5) 609-614. 

The oxidation of NADH and FADH2 by molecular oxygen is coupled in mitochondria to the endergonic synthesis of ATP from ADP and Pi. For many years the nature of the common intermediate between electron transport and ATP synthesis was elusive. Peter Mitchell, who received a Nobel Prize in chemistry in 1978 for his extraordinary insights, suggested that this common intermediate was the proton electrochemical potential. He proposed in the early... 

Amo, T, and M.D. Brand, 2007. Were inefficient mitochondrial haplogroups selected during migrations of modem humans A test using modular kinetic analysis of coupling in mitochondria from cybrid cell lines. Biochem. J. 404,345-351. 

Engelhardt s experiments in 1930 led to the notion that ATP is synthesized as the result of electron transport, and, by 1940, Severo Ochoa had carried out a measurement of the P/O ratio, the number of molecules of ATP generated per atom of oxygen consumed in the electron transport chain. Because two electrons are transferred down the chain per oxygen atom reduced, the P/O ratio also reflects the ratio of ATPs synthesized per pair of electrons consumed. After many tedious and careful measurements, scientists decided that the P/O ratio was 3 for NADH oxidation and 2 for succinate (that is, [FADHg]) oxidation. Electron flow and ATP synthesis are very tightly coupled in the sense that, in normal mitochondria, neither occurs without the other. 

The rate of respiration of mitochondria can be controlled by the availability of ADP. This is because oxidation and phosphorylation are tightly coupled ie, oxidation cannot proceed via the respiratory chain without concomitant phosphorylation of ADP. Table 12-1 shows the five conditions controlling the rate of respiration in mitochondria. Most cells in the resting state are in state 4, and respiration is controlled by the availability of ADP. When work is performed, ATP is converted to ADP, allowing more respiration to occur, which in turn replenishes the store of ATP. Under certain conditions, the concentration of inorganic phosphate can also affect the rate of functioning of the respiratory chain. As respiration increases (as in exercise). 

N-formyl-peptides (FP) are G-protein coupled receptors and members of the phagocyte chemotactic receptor family, which are involved in inflammatory processes. N-formyl-peptides are indicators of the presence of bacteria or damage to host cells in mitochondria. Receptor binding is giving a signal for infection... 

Blaustein We published a paper a couple of years ago on aortic smooth muscle stimulated with serotonin. Using moderate doses for short periods, which cause modest contraction, we saw no effect on Ca2+ in individual mitochondria. However, a big dose for a longer period causes the muscle to go into contracture, and there is a significant rise in Ca2+ in mitochondria. 

The transport systems of the inner mitochondrial membrane use various mechanisms. Metabolites or ions can be transported alone (uniport, U), together with a second substance (symport, S), or in exchange for another molecule (antiport. A). Active transport—i. e., transport coupled to ATP hydrolysis—does not play an important role in mitochondria. The driving force is usually the proton gradient across the inner membrane (blue star) or the general membrane potential (red star see p. 126). 

The energy producing reactions are coupled to carry out some other chemical reactions which are otherwise not energetically possible. ATP, ADP and AMP occur not only in cell cytosol but also in mitochondria and the nucleus. 

FIGURE 19-18 Coupling of electron transfer and ATP synthesis in mitochondria. In experiments to demonstrate coupling, mitochondria are suspended in a buffered medium and an 02 electrode monitors 02 consumption. At intervals, samples are removed and assayed for the presence of ATP. (a) Addition of ADP and P, alone results in little or no increase in either respiration (02 consumption black) or ATP synthesis (red). When succinate is added, respiration begins immediately and... 

During the 1940s, when it had become clear that formation of ATP in mitochondria was coupled to electron transport, the first attempts to pick the system apart and understand the molecular mechanism began. This effort led to the identification and at least partial characterization of several flavoproteins, iron-sulfur centers, ubiquinones, and cytochromes, most of which have been described in Chapters 15 and 16. It also led to the picture of mitochondrial electron transport shown in Fig. 10-5 and which has been drawn in a modem form in Fig. 18-5. 

The enzyme ATP synthase, formerly called F0FrATPase, makes most of the ATP, using ADP and inorganic phosphate, in mitochondria, eubacteria, and chloroplasts.91 The F0 component sits in the membrane and is connected to the Fj component, which is in the cytosol, by a 45-A-long stalk (the y subunit). The coupling of ATP synthesis to the flow of hydrogen ions across the membrane is done by the F0 part. The bovine F, complex is an assembly of five polypeptides, cr3, /33, y, 8, and e, of Mr 371 000. The three a and three /3 subunits are packed in a cylinder around the y, alternating a-/3-a-/3-a-/3.92... 

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