From OCR and ECAR to energy: Perspectives on the design and interpretation of bioenergetics studies

Abstract

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PD-L1 blockade liberates intrinsic antitumourigenic properties of glycolytic macrophages in hepatocellular carcinoma

“…We evaluated the extracellular acidification rate, which quantifies proton production as a surrogate for lactate production and thus reflects overall glycolytic flux. 19 In support, PD-L1 + macrophages exhibited substantially higher basal and maximal glycolytic rates compared with PD-L1macrophages (figure 1E). We also detected an obvious upregulation of glucose transporter Glut1 in PD-L1 + macrophages (figure 1F), suggesting an enhancement of glucose incorporation.…”

Sexually Dimorphic Effects of a Western Diet on Brain Mitochondrial Bioenergetics and Neurocognitive Function

“…Standardized mitochondrial oxygen consumption tests at supra-physiological concentrations of ADP can lead to misinterpretations of mitochondrial respiration because mitochondria rarely function in vivo at these extremely low ATP/ADP ratios [48]. Furthermore, mitochondrial energy transduction involves a network of dehydrogenases influencing cellular redox status [e.g., NAD(P)H/NAD(P)], electron transport chain proton pumping and establishment of the proton motive force, and the dissipation of this proton motive force during ATP synthesis based on energy demand (i.e., ATP/ADP ratio) [42,48].…”

“…Standardized mitochondrial oxygen consumption tests at supra-physiological concentrations of ADP can lead to misinterpretations of mitochondrial respiration because mitochondria rarely function in vivo at these extremely low ATP/ADP ratios [48]. Furthermore, mitochondrial energy transduction involves a network of dehydrogenases influencing cellular redox status [e.g., NAD(P)H/NAD(P)], electron transport chain proton pumping and establishment of the proton motive force, and the dissipation of this proton motive force during ATP synthesis based on energy demand (i.e., ATP/ADP ratio) [42,48]. A multi-dimensional diagnostic assessment is therefore required to best assess mitochondrial function under physiological ranges of ATP/ADP ratios.…”

An Economic Approach to Energy Budgets: How Many Resources Should Living Organisms Spare?

“…The evaluation of energy budgets requires quantities that can be (relatively easily) operationally assessed. For example, the cellular energy budget can be measured through different available techniques that facilitate the comparison of different cells, such as direct measurement, extracellular flux analysis, high-resolution respirometry, fluorescent dye kits (Schmidt et al, 2021), specific bioenergetic signatures such as respiration, glycolytic flux, Krebs cycle activity, ATP levels, total biomass, NAD(P)H, Ca2+, mitochondrial pH, membrane potential, redox state (Papkovsky and Zhdanov AV. 2021), the measure of changes in glycogen, lipid, and protein budgets (Smolders et al, 2003).…”

“…2021), aberrant expression/activity of proteins involved in ATP production (Zhdanov et al, 2011), etc. To provide an example, organisms exposed to suboptimal conditions (e.g., starvation, pharmacological treatment, diabetes, cancer) face an a priori cost of fighting stress in terms of metabolic resources (see, e.g., Smolders et al, 2003;Schmidt et al, 2021). The experiments concerning influence of energy availability on regulatory network dynamics usually evaluate how energy budgets affect both the microscopic cell behaviour (Kerr et al, 2019) and the mechanistic connections of sub-organismal processes.…”