M D Brand

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..They support the hypothesis that the formation of ketone bodies from acetyl-CoA may be regulated by the extent of succinylation of mitochondrial HMG-CoA synthase...

..Both definitions are valid, but they give different information. It is important to be aware of which definition is being used when analysing control coefficients in electron-transport chains and other group-transfer systems...

..We conclude that chloroform changes the measured H+/O as an artifact by causing mitochondrial breakage and does not cause measurable redox slip, whereas TMPD genuinely lowers H+/O...

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..The kinetics of electron transport through the cytochrome bc1 complex were not affected. Effects on cytochrome c oxidase were small or nonexistent...

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..UCP1 catalyses a regulated inducible proton conductance in brown adipose tissue and the possibility remains open that UCP2 and UCP3 have a similar role in other tissues, although this has yet to be demonstrated...

..This may be an important control mechanism in ketogenesis...

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..Conversely, it could be seen that the failure of adrenaline to maintain a constant glucose 6-phosphate concentration was due to the stimulation of glycogen breakdown and inhibition of glucose release...

..Thus mild uncoupling may be particularly significant for ROS production from complex I on the matrix side of the mitochondrial inner membrane...

..The application of modular control analysis to microarray data in order to partition and quantify the importance of mRNA clusters in mediating responses is described...

..The approach allows a quantitative description of the relative importance of signal transduction pathways and the routes by which they activate a specific cellular process. It should be widely applicable...

..Thus, the fraction of cellular respiration devoted to different processes remained constant and the cellular energy balance was preserved in the hypometabolic state...

..However, to date there is no direct evidence in cells or organisms that mitochondrial proton cycling lowers ROS production or oxidative damage or that it increases lifespan...

..UCPs may also integrate inputs from different fuels in pancreatic beta-cells and modulate insulin secretion. They are exciting potential targets for treatment of obesity, cachexia, aging and diabetes...

..However, ATP use by the F(1)F(0)-ATPase is limited in anoxia by a profound inhibition of the enzyme. Even so, ATP use by the F(1)F(0)-ATPase might account for approximately 9% of the ATP turnover in anoxic frog skeletal muscle...

..Carp and zebrafish are ectotherms--they do not raise their body temperatures above ambient by producing excess heat. The presence of UCP2 in these fish thus suggests the protein may have function(s) not related to thermogenesis...

..AMP activation of ANT could be important for physiological regulation of metabolic rate...

..This suggests that pH and state change affect metabolic depression by similar mechanisms but that the metabolic depression by hypoxia involves a separate mechanism...

..It discusses the ways the approach has been used in organelles and cells to identify the sites of action of effectors, to measure the distribution of control by blocks of reactions, and to measure regulation by effectors...

..These results are discussed in the context of competing theories to explain the metabolism-body size allometry, and are found to support the 'allometric cascade' model...

..2, similar to the exponent in mammalian hepatocytes. However, unlike mammals, liver mitochondrial proton conductance in ectotherms showed no allometric relationship with body size...

..Specific uncoupling of muscle or brown adipocyte mitochondria remains an attractive target for the development of antiobesity drugs...

..Thus the lower mitochondrial respiration rate in hepatopancreas cells from aestivating snails was not caused by differences in mitochondrial volume or surface density but was associated with intrinsic changes in the mitochondria...

..We conclude that CoQ acted in mitochondria through production of superoxide, which mediated uncoupling, probably by acting through uncoupling protein 2...

..These observations suggest that uncoupling of yeast mitochondria by UCP2 is an overexpression artifact leading to compromised mitochondrial integrity...

..The physiological role of the proton leak, and of the uncoupling protein 1 homologues, remains similarly unclear...

..This provides evidence that skeletal muscle UCP-3 has the potential to influence metabolic rate and glucose homeostasis in the whole animal...