The causes and functions of mitochondrial proton leak

Brand, Martin D.; Chien, Lee-Feng; Ainscow, Edward; Rolfe, David F. S.; Porter, Richard K.

doi:10.1016/0005-2728(94)90099-x

Cited by 454 publications

(328 citation statements)

References 30 publications

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“…The kinetic response of the proton-conductance pathway to its driving force (membrane potential) can therefore be measured as the relationship between respiration rate and mitochondrial membrane potential when the potential is varied by titration with electron-transport-chain inhibitors [2,3,16,17]. We determined respiration rate and membrane potential simultaneously using electrodes sensitive to oxygen and to the potential-dependent probe triphenylmethyl phosphonium cation (TPMP + ) [3,18]. Mitochondria (0.5 mg of protein\ml) were incubated in assay medium containing 5 µM rotenone, 1 µg\ml oligomycin and 80 ng\ml nigericin (to collapse the difference in pH across the inner membrane).…”

Section: Measurement Of Proton Conductancementioning

confidence: 99%

“…The resulting electrochemical proton gradient performs useful work when protons re-enter the matrix through the F o F " -ATPase (causing synthesis of ATP from ADP and P i [1]) or through other proteins to drive ion and substrate transport. However, the electrochemical proton gradient can also be dissipated by leak reactions catalysed by endogenous mitochondrial proton-conductance pathways [2][3][4][5]. In the absence of oxidative phosphorylation, all the protons pumped by the respiratory chain out of the mitochondria return by this proton leak, and there is oxygen consumption without coupled ATP synthesis.…”

Section: Introductionmentioning

confidence: 99%

“…Both can be assayed reliably by measuring their kinetics [2,3]. Basal proton conductance is found in all mitochondria.…”

Section: Introductionmentioning

confidence: 99%

“…It is responsible for 50 % of the respiration of resting perfused rat skeletal muscle [7], and for 35 % of the respiration of a maximally stimulated hindlimb muscle model [8]. The basal proton conductance in all rat tissues causes up to 20-25 % of standard metabolic rate [3,7,8]. Inducible proton conductance occurs through specific uncoupling proteins, and is tightly regulated.…”

Section: Introductionmentioning

confidence: 99%

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Effects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria

Cadenas

Brand

2000

Biochemical Journal

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During oxidative phosphorylation most of the protons pumped out to the cytosol across the mitochondrial inner membrane return to the matrix through the ATP synthase, driving ATP synthesis. However, some of them leak back to the matrix through a proton-conductance pathway in the membrane. When the ATP synthase is inhibited with oligomycin and ATP is not being synthesized, all of the respiration is used to drive the proton leak. We report here that Mg# + inhibits the proton conductance in rat skeletal-muscle mitochondria. Addition of Mg# + inhibited both oligomycin-inhibited respiration and the proton conductance, while removal of Mg# + using EDTA activated these processes. The proton conductance was inhibited by more than 80 % as free Mg# + was raised from 25 nM to 220 µM. Half-maximal inhibition occurred at about 1 µM free Mg# + ,

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Section: Measurement Of Proton Conductancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Both can be assayed reliably by measuring their kinetics [2,3]. Basal proton conductance is found in all mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria

Cadenas

Brand

2000

Biochemical Journal

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“…This leak occurs via agents called uncoupling proteins (UCPs). This process, which is linearly dependent on membrane potential, may consume up to 20-25% of resting metabolism (Brand et al 1994) in various tissues and species, including endotherms and ectotherms (Stuart et al 2001). It has been suggested that proton leak must be extremely important, since it occurs at the expense of a high proportion of energy production (Brand 2000).…”

Section: Discussionmentioning

confidence: 99%

Energetics and longevity in birds

Furness

Speakman

2008

AGE

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The links between energy expenditure and ageing are different at different levels of enquiry. When studies have examined the relationships between different species within a given class the association is generally negative-animals with greater metabolism per gram of tissue live shorter lives. Within species, or between classes (e.g. between birds and mammals) the association is the opposite-animals with higher metabolic rates live longer. We have previously shown in mammals that the negative association between lifespan and metabolic rate is in fact an artefact of using resting rather than daily energy expenditure, and of failing to adequately take into account the confounding effects of body size and the lack of phylogenetic independence of species data. When these factors are accounted for, across species of mammals, the ones with higher metabolism also have the largest lifetime expenditures of energy-consistent with the inter-class and intra-specific data. A previous analysis in birds did not yield the same pattern, but this may have been due to a lack of sufficient power in the analysis. Here we present an analysis of a much enlarged data set (>300 species) for metabolic and longevity traits in birds. These data show very similar patterns to those in mammals. Larger individuals have longer lives and lower per-gram resting and daily energy expenditures, hence there is a strong negative relationship between longevity and mass-specific metabolism. This relationship disappears when the confounding effects of body mass and phylogeny are accounted for. Across species of birds, lifetime expenditure of energy per gram of tissue based on both daily and resting energy expenditure is positively related to metabolic intensity, mirroring these statistical relationships in mammals and synergising with the positive associations of metabolism with lifespan within species and between vertebrate classes.

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O2 consumption and metabolic activities in resting cardiac myocytes from rainbow trout

Mortensen

Gesser

1999

J. Exp. Zool.

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The causes and functions of mitochondrial proton leak

Cited by 454 publications

References 30 publications

Effects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria

Effects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria

Energetics and longevity in birds

O2 consumption and metabolic activities in resting cardiac myocytes from rainbow trout

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