Salin 2018 Integr Comp Biol
|Salin K, Villasevil EM, Anderson GJ, Selman C, Chinopoulos C, Metcalfe NB (2018) The RCR and ATP/O indices can give contradictory messages about mitochondrial efficiency. Integr Comp Biol 58:486-94.|
Abstract: Mitochondrial efficiency is typically taken to represent an animal's capacity to convert its resources into ATP. However, the term mitochondrial efficiency, as currently used in the literature, can be calculated as either the respiratory control ratio, RCR (ratio of mitochondrial respiration supporting ATP synthesis to that required to offset the proton leak) or as the amount of ATP generated per unit of oxygen consumed, ATP/O ratio. The question of how flexibility in mitochondrial energy properties (i.e. in rates of respiration to support ATP synthesis and offset proton leak, and in the rate of ATP synthesis) affects these indices of mitochondrial efficiency has tended to be overlooked. Furthermore, little is known of whether the RCR and ATP/O ratio vary in parallel, either among individuals or in response to environmental conditions. Using data from brown trout Salmo trutta we show that experimental conditions affect mitochondrial efficiency, but the apparent direction of change depends on the index chosen: a reduction in food availability was associated with an increased RCR (i.e. increased efficiency) but a decreased ATP/O ratio (decreased efficiency) in liver mitochondria. Moreover, there was a negative correlation across individuals held in identical conditions between their RCR and their ATP/O ratio. These results show that the choice of index of mitochondrial efficiency can produce different, even opposing, conclusions about the capacity of the mitochondria to produce ATP. Neither ratio is necessarily a complete measure of efficiency of ATP production in the living animal (RCR because it contains no assessment of ATP production, and ATP/O because it contains no assessment of respiration to offset the proton leak). Consequently, we suggest that a measure of mitochondrial efficiency obtained nearer to conditions where respiration simultaneously offsets the proton leak and produce ATP would be sensitive to changes in both proton leakage and ATP production, and is thus likely to be more representative of the state of the mitochondria in vivo.
Gnaiger E 2022-02-22
- "However, the term mitochondrial efficiency, as currently used in the literature, can be calculated as either the respiratory control ratio, RCR (ratio of mitochondrial respiration supporting ATP synthesis to that required to offset the proton leak) or as the amount of ATP generated per unit of oxygen consumed, ATP/O ratio." - This reference to 'the term mitochondrial efficiency, as currently used in the literature' ignores the literature on chemical engineering and the thermodynamics of irreversible processes. To avoid confusion of terms: (1) The classical RCR should not be referred to as an expression of efficiency, because it is a ratio of respiratory fluxes with a lower boundary of 1 and a maximum of infinity. 1/RCR is a more useful expression in this context, although 1/RCR=0 relates to maximum flux efficiency and 1/RCR=1 indicates a flux efficiency of zero. This problem is solved by expressing flux efficiency as 1-1/RCR (Gnaiger 2020 MitoPathways). Then 1-1/RCR and ATP/O2 ratios point into the same direction, and the apparent discrepancy alluded to in the title is solved. (2) Likewise, the ATP/O ratio is a flux ratio without boundaries from 0 to 1. Flux efficiencies and force efficiencies are properly normalized to obtain maximum efficiencies of 1 (or 100 %) and minimum efficiencies of 0.
- "little is known of whether the RCR and ATP/O ratio vary in parallel" - A complete analysis is available:
- Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - »Bioblast link«
- Further reading: Rasmussen HN, Rasmussen UF (1997) Small scale preparation of skeletal muscle mitochondria, criteria of integrity, and assays with reference to tissue function. Mol Cell Biochem 174:55-60.
- "the choice of index of mitochondrial efficiency can produce different, even opposing, conclusions about the capacity of the mitochondria to produce ATP" - Yes, even if we use 1/RCR instead of RCR, this apparently 'opposing' effect emerges. We should not turn a mathematical triviality into a trivial biological terminology. If we consider RCR = P/L (OXPHOS capacity over LEAK respiration), then the P-L control efficiency is defined as jP-L = (P-L)/P = 1-L/P = 1-1/RCR. P»/O2 ratios (ADP/O2 or ATP/O2 or Pi/O2 ratios) increase with increasing jP-L − they give consistent messages.
- Further notes
- p 487: "the amount of energy produced by the system" - Take care of the First Law of thermodynamics.
- Figure 3a and 3d and Figure 4: The theoretically non-linear relationship (Gnaiger 2001) was fitted by linear regression in partitioned ranges in these figures. This obscures the underlying concept.
- Cardoso et al (2021) Magnesium Green for fluorometric measurement of ATP production does not interfere with mitochondrial respiration. Bioenerg Commun 2021.1. doi:10.26124/bec:2021-0001
Labels: MiParea: Respiration, Comparative MiP;environmental MiP, mt-Awareness
Organism: Fishes Tissue;cell: Liver Preparation: Homogenate
Regulation: ATP production Coupling state: LEAK, OXPHOS Pathway: N, S, NS, ROX HRR: Oxygraph-2k
Labels, 2018-08, MgG, MitoFit 2021 MgG