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| |description='''Flux control ratios''' express respiratory control independent of mitochondrial content and cell size. FCR are normalized for maximum flux in a common reference state, to obtain theoretical lower and upper limits of 0.0 and 1.0 (0% and 100%). | | |description='''Flux control ratios''' express respiratory control independent of mitochondrial content and cell size. FCR are normalized for maximum flux in a common reference state, to obtain theoretical lower and upper limits of 0.0 and 1.0 (0% and 100%). |
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| 1. ROX/Eβ: The ROX/Eβ ratio is low (0.01 to 0.07; Tab. 1), but ROX contributes to a
| | #'''ROX/Eβ''': The ROX/Eβ ratio. |
| significant extent to LEAK respiration, with corresponding ROX/Lβ ratios ranging from
| | #'''L/E:''' The LEAK control ratio. |
| 0.1 to 0.3, and up to 0.5 in growth-arrested fibroblasts (Tab. 1).
| | #'''R/E:''' The ROUTINE control ratio. |
| 2. L/E: The LEAK control ratio is the ratio of LEAK respiration and ETS capacity. L/E
| | #'''(R-L)/E:''' The netROUTINE control ratio. |
| ranges from 0.09 to 0.14 in various cells (Tab. 1; the inverse, 11 to 7, is the respiratory
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| control ratio, RCR; ref. 1,11). Dyscoupling increases the L/E ratio, e.g. to 0.21 in
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| senescent fibroblasts (Tab. 1). Alternatively, the L/E ratio may increase without intrinsic
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| uncoupling or dyscoupling, if ETS capacity is diminished. It is, therefore, important to
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| evaluate potential defects of ETS capacity per mt-marker, e.g. ETS per citrate synthase
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| activity (5,8,11).
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| 3. R/E: The ROUTINE control ratio is the ratio of (coupled) ROUTINE respiration and (noncoupled)
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| ETS capacity. R/E ranges from 0.2 to 0.4 (Tab. 1; the inverse of 5 to 2.5 is the
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| uncoupling control ratio, UCR; ref. 3-8). The R/E ratio is an expression of how close
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| ROUTINE respiration operates to ETS capacity. Reported R/E ratiosοΏ½0.5 (15) could not
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| be reproduced by HRR in a wide range of human cell types and incubation conditions (Tab.
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| 1). The discrepancies cannot be fully explained by high glucose concentrations in culture
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| and respiration media, since glucose exerts an effect not only on R but also on E (13). R/E
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| ratios increase due to (i) high ATP demand and ADP-stimulated ROUTINE respiration, (ii)
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| dyscoupling (senescent fibroblasts; Tab. 1), and (iii) limitation of respiratory capacity by
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| defects of substrate oxidation and complexes of the ETS.
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| 4. (R-L)/E: The netROUTINE control ratio, (R-L)/E, expresses phosphorylation-related
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| respiration (corrected for LEAK respiration) as a fraction of ETS capacity. 0.1 to 0.3 of
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| ETS capacity is used for oxidative phosphorylation under ROUTINE conditions (Tab. 1).
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| (R-L)/E remains constant, if dyscoupling is fully compensated by an increase of ROUTINE
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| respiration and a constant rate of oxidative phosphorylation is maintained (fibroblasts in
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| Tab. 1). Upon stimulation of OXPHOS by an increased ATP demand, or if the respiratory
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| capacity declines without effect on the rate of OXPHOS, however, (R-L)/E increases,
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| which indicates that a higher proportion of the maximum capacity is activated to drive
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| ATP synthesis. (R-L)/E declines to zero in either fully uncoupled cells (R=L=E) or in cells
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| under metabolic arrest (R=L<E).
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| 5. If the PC protocol is extended by measurement of cytochrome c oxidase, then the ratio of
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| CIV activity and non-coupled respiration is an index of the apparent excess capacity of this
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| enzyme step in the ETS. Autooxidation of ascorbate and TMPD (Tab. 2) is extremely high
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| in culture media, hence a mitochondrial respiration medium is used (5).
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| |info=[[MiPNet12.15]]; [[Pesta_2010_Protocol]] | | |info=[[MiPNet12.15]]; [[Pesta_2010_Protocol]] |
| |type=Respiration | | |type=Respiration |
- high-resolution terminology - matching measurements at high-resolution
Flux control ratio
Description
Flux control ratios express respiratory control independent of mitochondrial content and cell size. FCR are normalized for maximum flux in a common reference state, to obtain theoretical lower and upper limits of 0.0 and 1.0 (0% and 100%).
- ROX/Eβ: The ROX/Eβ ratio.
- L/E: The LEAK control ratio.
- R/E: The ROUTINE control ratio.
- (R-L)/E: The netROUTINE control ratio.
Abbreviation: FCR
Reference: MiPNet12.15; Pesta_2010_Protocol
Labels:
Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Flux Control; Additivity; Threshold; Excess Capacity"Flux Control; Additivity; Threshold; Excess Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.