Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate

Rolfe, David F. S.; Brand, Martin D.

doi:10.1152/ajpcell.1996.271.4.c1380

Cited by 285 publications

(199 citation statements)

References 20 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…The publications of two papers in 1996 prompted several laboratories to search for mitochondrial UCP and/or UCP homologues in skeletal muscle and other tissues, namely, (i) the report by Nagase et al [34] claiming that treatment with a h3 agonist led to weight loss associated with expression of an uncoupling protein detected in skeletal muscle and white adipose tissue by Northern and Western probing for the BAT-UCP, and (ii) the report of Rolfe and Brand [35] that the phenomenon of mitochondrial dproton leakT is not unique to BAT, as originally thought, but also exists in tissues other than BAT, and could contribute as much as 25-50% of the liver and skeletal muscle heat production at rest.…”

Section: Novel Duncouplingt Proteinsmentioning

confidence: 99%

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Dulloo

Seydoux

Jacquet

2004

Physiology & Behavior

View full text Add to dashboard Cite

After decades of controversies about the quantitative importance of autoregulatory adjustments in energy expenditure in weight regulation, there is now increasing recognition that even subtle variations in thermogenesis could, in dynamic systems and over the long term, be important in determining weight maintenance in some and obesity in others. The main challenge nowadays is to provide a mechanistic explanation for the role of adaptive thermogenesis in attenuating and correcting deviations of body weight and body composition, and in the identification of molecular mechanisms that constitute its effector systems. This workshop paper reconsiders what constitutes adaptive changes in thermogenesis and reassesses the role of the sympathetic nervous system (SNS) and uncoupling proteins (UCP1, UCP2, UCP3, UCP5/BMCP1) as the efferent and effector components of the classical one-control system for adaptive thermogenesis and fat oxidation. It then reviews the evidence suggesting that there are in fact two distinct control systems for adaptive thermogenesis, the biological significance of which is to satisfy-in a lifestyle of famine-and-feast-the needs to suppress thermogenesis for energy conservation during weight loss and weight recovery even under environmental stresses (e.g., cold, infection, nutrient imbalance) when sympathetic activation of thermogenesis has equally important survival value.Keywords: Obesity; Diabetes; Cachexia; Catecholamines; UCP Resistance to obesity in an obesigenic environmentOne of the greatest challenges towards understanding the aetiology of human obesity is to explain how in environments that promote overeating of high-fat foods and discourage physical activity, there is always a section of the population who, apparently without conscious effort, do not become obese. How do they resist obesity? How is constancy of body weight achieved over decades in these individuals? In addressing the issue of human susceptibility to leanness and fatness, there are three cardinal features of body weight regulation that need to be underlined: (i) Humans cannot escape the laws of thermodynamics.Whatever theory is put forward to explain body weight and body composition regulation, it is undeniable that changes in body energy stores (and ultimately body weight) cannot occur unless there is a difference between energy intake and energy expenditure. (ii) Subtle perturbations in energy balance can lead to obesity. To put it another way, long-term constancy of body weight can only be achieved if the matching between energy intake and energy expenditure is extremely precise, since an error of only 1% between input and output of energy, if persistent, will lead to a gain or loss of 1 kg per year or some 40 kg between the age of 20 to 60 years. Yet, a difference of 5% between energy intake and energy expenditure is hardly measurable with available techniques. (iii) Body weight is a fluctuating and oscillatory phenomenon. Even in individuals that maintain a relatively stable lean body weight over decades, the...

show abstract

Section: Novel Duncouplingt Proteinsmentioning

confidence: 99%

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Dulloo

Seydoux

Jacquet

2004

Physiology & Behavior

View full text Add to dashboard Cite

show abstract

“…The observation that mitochondria still consume oxygen when ADP phosphorylation is inhibited demonstrates that the coupling of respiration to ATP synthesis is imperfect ; in fact, State 4 respiration is mainly due to uncoupling [19,20]. The coupling of oxidative phosphorylation is impaired by the existence of certain leaks through the mitochondrial inner membrane [19][20][21][22][23][24][25][26].…”

Section: Uncoupling Of Respirationmentioning

confidence: 99%

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Ricquier¹,

Bouillaud

2000

Biochemical Journal

610

115

View full text Add to dashboard Cite

Animal and plant uncoupling protein (UCP) homologues form a subfamily of mitochondrial carriers that are evolutionarily related and possibly derived from a proton\anion transporter ancestor. The brown adipose tissue (BAT) UCP1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identified in plants are induced in a cold environment and may be involved in resistance to chilling. The biochemical activities and biological functions of the recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respiration uncoupling and proton leaks in mitochondria. Moreover, genetic studies suggest that UCP2 and UCP3 play a part in

show abstract

“…Its mechanism and regulation are unclear, but the evidence that it is catalysed by specific uncoupling proteins is weak [4][5][6]. 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].…”

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%

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

Cadenas

Brand

2000

Biochemical Journal

View full text Add to dashboard Cite

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# + ,

show abstract

Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate

Cited by 285 publications

References 20 publications

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

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

Contact Info

Product

Resources

About