The RCR and ATP/O Indices Can Give Contradictory Messages about Mitochondrial Efficiency

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.

Integrating Mitochondrial Aerobic Metabolism into Ecology and Evolution

“…3A). Respiration rates indicate potential metabolic capacity levels, while efficiency proxies indicate how efficient mitochondria are at producing ATP [81,82]. Both are likely to be relevant for organismal performance, but the in vivo relevance of such in vitro measurements must be carefully considered.…”

“…The open circles represent the in vitro measurements of OXPHOS (iii) or LEAK (iv) respiration (Box 1), though these extremes would not occur in vivo; it is worth noting that using these extremes to calculate the proportion of oxygen resulting in proton leak (i.e. RCR; Box 1) would result in an misleading estimate of the actual proportions of oxygen resulting in leak or ATP production at either during either high or low activity [80,81]. In (B), within-and among-individual variation in mitochondrial efficiency is illustrated by tracing hypothetical relative proportions of different endpoints of mitochondrial oxygen consumption during states of high or low demand for ATP.…”

Adjustments of cardiac mitochondrial phenotype in a warmer thermal habitat is associated with oxidative stress in European perch, Perca fluviatilis

“…With the respiration rates measured above, the P I /L I ratio at the level of complex I (CI − OXPHOS/CI-LEAK), as well as the E I+II /P I+II ratio (CI + CII-ETS/ CI + CII-OXPHOS) were calculated. The P I /L I ratio represents the mitochondrial respiration supporting ATP synthesis to that required to offset the proton leak and is indicative of mitochondrial quality and of mitochondrial coupling 50 , 71 . The E I+II /P I+II ratio is an expression of the limitation of OXPHOS capacity by the phosphorylation system 50 .…”

SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing

“…Uncoupling thus plays an important role in mitochondrial efficiency, which can either be defined as the respiratory control ratio (RCR - ratio of mitochondrial respiration supporting ATP synthesis to that required to offset the proton leak) or the ATP/oxygen ratio (the amount of ATP generated per unit of oxygen consumed) – this can lead to some confusion, as it can lead to opposite conclusions about efficiency. However, whichever metric is used, it does describe the capacity to convert resources into ATP, and in effect, the coupling efficiency [ 147 ]. In fact a study has shown that skeletal muscle mitochondria in obese, sedentary and insulin resistance women somewhat paradoxically show reduced mitochondrial coupling, but a higher production of mitochondrial hydrogen peroxide.…”