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Difference between revisions of "Flux control ratio"

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(Created page with "{{MitoPedia |abbr=FCR |description='''Flux control ratios''' express respiratory control independent of mitochondrial content and cell size. FCR are normalized for maximum flux i...")
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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%).


1. ROX/E’: The ROX/E’ ratio is low (0.01 to 0.07; Tab. 1), but ROX contributes to a
#'''ROX/E’''': The ROX/E’ ratio.
significant extent to LEAK respiration, with corresponding ROX/L’ 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
senescent fibroblasts (Tab. 1). Alternatively, the L/E ratio may increase without intrinsic
uncoupling or dyscoupling, if ETS capacity is diminished. It is, therefore, important to
evaluate potential defects of ETS capacity per mt-marker, e.g. ETS per citrate synthase
activity (5,8,11).
3. R/E: The ROUTINE control ratio is the ratio of (coupled) ROUTINE respiration and (noncoupled)
ETS capacity. R/E ranges from 0.2 to 0.4 (Tab. 1; the inverse of 5 to 2.5 is the
uncoupling control ratio, UCR; ref. 3-8). The R/E ratio is an expression of how close
ROUTINE respiration operates to ETS capacity. Reported R/E ratiosοΏ½0.5 (15) could not
be reproduced by HRR in a wide range of human cell types and incubation conditions (Tab.
1). The discrepancies cannot be fully explained by high glucose concentrations in culture
and respiration media, since glucose exerts an effect not only on R but also on E (13). R/E
ratios increase due to (i) high ATP demand and ADP-stimulated ROUTINE respiration, (ii)
dyscoupling (senescent fibroblasts; Tab. 1), and (iii) limitation of respiratory capacity by
defects of substrate oxidation and complexes of the ETS.
4. (R-L)/E: The netROUTINE control ratio, (R-L)/E, expresses phosphorylation-related
respiration (corrected for LEAK respiration) as a fraction of ETS capacity. 0.1 to 0.3 of
ETS capacity is used for oxidative phosphorylation under ROUTINE conditions (Tab. 1).
(R-L)/E remains constant, if dyscoupling is fully compensated by an increase of ROUTINE
respiration and a constant rate of oxidative phosphorylation is maintained (fibroblasts in
Tab. 1). Upon stimulation of OXPHOS by an increased ATP demand, or if the respiratory
capacity declines without effect on the rate of OXPHOS, however, (R-L)/E increases,
which indicates that a higher proportion of the maximum capacity is activated to drive
ATP synthesis. (R-L)/E declines to zero in either fully uncoupled cells (R=L=E) or in cells
under metabolic arrest (R=L<E).
5. If the PC protocol is extended by measurement of cytochrome c oxidase, then the ratio of
CIV activity and non-coupled respiration is an index of the apparent excess capacity of this
enzyme step in the ETS. Autooxidation of ascorbate and TMPD (Tab. 2) is extremely high
in culture media, hence a mitochondrial respiration medium is used (5).
|info=[[MiPNet12.15]]; [[Pesta_2010_Protocol]]
|info=[[MiPNet12.15]]; [[Pesta_2010_Protocol]]
|type=Respiration
|type=Respiration

Revision as of 08:10, 14 September 2010


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%).

  1. ROX/E’: The ROX/E’ ratio.
  2. L/E: The LEAK control ratio.
  3. R/E: The ROUTINE control ratio.
  4. (R-L)/E: The netROUTINE control ratio.

Abbreviation: FCR

Reference: MiPNet12.15; Pesta_2010_Protocol


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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.