Gnaiger 2009 Int J Biochem Cell Biol

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Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45.

» PMID: 19467914 Bioblast pdf

Gnaiger E (2009) Int J Biochem Cell Biol

Fig. 1. Substrate control of electron flow to oxygen through Complex I or Complex II separately (N- or S-pathway), or simultaneously (NS) in mitochondrial preparations. Substrate supply restricted to pyruvate&malate, PM, or succinate&rotenone, S(Rot), exerts artificial upstream control of flux through the linear electron transport chain (ETC). With PM (or GM) as substrates, metabolite depletion (loss of citrate, isocitrate, 2-oxoglutarate and succinate from the matrix) prevents substrate supply to CII. With succinate as the only substrate, blockage of CI is necessary to prevent inhibition of succinate dehydrogenase by accumulating oxaloacetate. Combined NS substrate supply with simultaneous electron entry at the Q-junction exerts an additive effect on total electron flux through the convergent Electron transfer-pathway (ET-pathway). This shifts control of flux downstream towards Complexes III and IV, and towards the phosphorylation system in oxidative phosphorylation. Convergent electron flow corresponds to the operation of the tricarboxylic acid cycle in the intact cell, generating simultaneously NADH and succinate in the matrix as substrates for NS-pathway control. This physiological state is reconsituted in mitochondrial preparations by external NS-substrate supply (PMS; or substituting pyruvate by glutamate, GMS or GS). Substrate entry across the inner mitochondrial membrane into the mitochondrial matrix space is shown by dotted arrows (metabolite depletion from the matrix is not shown). Full arrows indicate flow of electron pairs (single arrows) split into flow of single electrons (double arrows) (after Gnaiger 2009).
Maximal ADP-stimulated mitochondrial respiration depends on NS-convergent electron flow through Complexes I&II to the Q-junction of the electron transport system (ET-pathway). In most studies of respiratory control in mitochondrial preparations, however, respiration is limited artificially by supplying N- or S-substrates for electron input through either Complex I or II. High-resolution respirometry with minimal amounts of tissue biopsy (1 to 3 mg wet weight of permeabilized muscle fibres per assay) provides a routine approach for multiple substrate-uncoupler-inhibitor titrations. Under physiological conditions, maximal respiratory capacity is obtained with glutamate&malate&succinate, reconstituting the operation of the tricarboxylic acid cycle and preventing depletion of key metabolites from the mitochondrial matrix. In human skeletal muscle, conventional assays with pyruvate&malate or glutamate&malate yield submaximal oxygen fluxes at 0.50 to 0.75 of capacity of oxidative phosphorylation (OXPHOS). Best estimates of muscular OXPHOS capacity at 37 °C [pmol O2∙s­-1∙mg-1 wet weight] with isolated mitochondria or permeabilized fibres, suggest a range of 100 to 150 and up to 180 in healthy humans with normal body mass index and top endurance athletes, but reduction to 60 to 120 in overweight healthy adults with predominantly sedentary life style. The apparent ET-pathway excess capacity (noncoupled respiration) over ADP-stimulated OXPHOS capacity is high in skeletal muscle of active and sedentary humans, but absent in mouse skeletal muscle. Such differences of mitochondrial quality in skeletal muscle are unexpected and cannot be explained at present. A comparative data base of mitochondrial physiology may provide the key for understanding the functional implications of mitochondrial diversity from mouse to man, and evaluation of altered mitochondrial respiratory control patterns in health and disease.

Keywords: Q-junction, Q-cycle, Pyruvate, Glutamate, Succinate, Tricarboxylic acid cycle

O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck Oroboros


  • 2017: For further clarification, NADH-linked respiration (N-respiration; CI-linked) and succinate-linked respiration (S-respiration; CII-linked) are distinguished from combined NS-respiration (CI&II-linked).


  • Table 2, ref c(1) Ponsot et al. (2005). - The correct reference is Ponsot et al. (2006).
  • Ponsot E, Dufour SP, Zoll J, Doutrelau S, N'Guessan B, Geny B, Hoppeler H, Lampert E, Mettauer B, Ventura-Clapier R, Richard R (2006) Exercise training in normobaric hypoxia in endurance runners. II. Improvement of mitochondrial properties in skeletal muscle. J Appl Physiol (1985) 100:1249-57. - »Bioblast link«

MitoPedia: BME


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MitoPedia: BME

BME and mitObesity
BME cutoff pointsBME cutoffCutoff points for body mass excess, BME cutoff points, define the critical values for underweight, overweight, obesity and various degrees of obesity. BME cutoffs are calibrated by crossover-points of BME with established BMI cutoffs. The underweight and severe underweight cutoff points are BME = -0.1 and -0.2. The overweight cutoff is BME = 0.2. Increasing degrees of obesity are defined by BME cutoffs of 0.4, 0.6, 0.8, and above.
Body fat excessBFEBody fat is conventionally expressed as BF%, which is the percentage of body fat mass relative to the total body mass. In the healthy reference population (HRP), there is zero body fat excess, and the fraction of excess body fat in the HRP is expressed - by definition - relative to the reference body mass, M°, at any given height. Although M° is identical in females and males at any given height, the fraction of body fat is higher in females than males in the HRP, hence it is reasonable that the body fat excess, BFE, - but not BF% - represents the common risk factor and indicator of obesity. Importantly, body fat excess and body mass excess, BME, are linearly related, which is not the case for the body mass index, BMI.
Body massM [kg·x-1]The body mass, M, is the mass [kg] of an individual (object) [x] and is expressed in units [kg/x]. The SI unit for mass (of a system), m, is [kg] (1 kg = 1000 g). The individual (object) is a countable quantity, therefore, the unit [x] is a dimensionless number. Whereas the body weight changes as a function of gravitational force (you are weightless at zero gravity; your floating weight in water is different from your weight in air), your mass is independent of gravitational force, and it is the same in air and water.
Body mass excessBMEThe body mass excess, BME, is an index of obesity and as such BME is a lifestyle metric. The BME with respect to the healthy reference population, HRP, is defined as BME ΔM/M°. ΔM is the excess body mass exceeding the reference body mass, M°, in the HRP. Thus the BME is a measure of the extent to which your actual body mass, M [kg/x], deviates from M° [kg/x], which is the reference body mass [kg] per individual [x] without excess body fat. The BME is expressed relative to the reference body mass for your height, H [m]. A balanced BME is BME° = 0.0 with a band width of -0.1 towards underweight and +0.2 towards overweight.
Gnaiger 2019 MiP2019
Healthy reference populationHRPA healthy reference population, HRP, of zero underweight or overweight is considered as a standard population. The WHO Child Growth Standards on height and body mass refer to healthy girls and boys from Brazil, Ghana, India, Norway, Oman and the USA. The Committee on Biological Handbooks compiled data on height and body mass of healthy males from infancy to old age (USA), published before emergence of the fast-food and soft drink epidemic. Four allometric phases are distinguished with different allometric exponents. At heights above 1.26 m the allometric exponent is 2.9, equal in women and men, and significantly different from the BMI [kg/m2] exponent of 2.
Height of humansH [m]The height of humans, H, is given in SI units in meters [m]. Without further identifyer, H is considered as the standing height, measured without shoes, hair ornaments and heavy outer garments.
VO2maxVO2max; VO2max/MMaximum oxygen consumption, VO2max, is measured by spiroergometry on human and animal organisms capable of controlled physical exercise performance on a treadmill or cycle ergometer. VO2max is the maximum respiration of an organism, expressed as the volume of O2 at STPD consumed per unit of time per individual object [mL.min-1.x-1]. If normalized per body mass of the individual object, M [kg.x-1], mass specific maximum oxygen consumption, VO2max/M, is expressed in units [].

Further references

» MitoPedia: Respiratory states OXPHOS ROUTINE ET-capacity LEAK  - ROX
» O2k-Publications: Human - Skeletal muscle
» O2k-Publications: Q-junction effect

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Exercise physiology;nutrition;life style, mt-Medicine  Pathology: Aging;senescence, Obesity 

Organism: Human, Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue, Isolated mitochondria  Enzyme: Marker enzyme  Regulation: Coupling efficiency;uncoupling  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k