From Bioblast
Donnelly 2022 MitoFit Hypoxia
| Donnelly C, Schmitt S, Cecatto C, Cardoso LHD, Komlodi T, Place N, Kayser B, Gnaiger E (2022) The ABC of hypoxia – what is the norm. https://doi.org/10.26124/mitofit:2022-0025.v2 — 2022-11-14 published in Bioenerg Commun 2022.12. |
» MitoFit Preprints 2022.25.v2.
The ABC of hypoxia – what is the norm 
MitoFit Preprints (2022) MitoFit Prep
Abstract:
- Version 2 (v2) 2022-07-15 The ABC of hypoxia – what is the norm https://doi.org/10.26124/mitofit:2022-0025.v2
- Version 1 (v1) 2022-06-28 - »Link to all versions«
Donnelly 2022 Abstract Bioblast: Hypoxia is a condition of oxygen levels below normoxia and opposite to hyperoxia. We here define the normoxic reference state by three complementary precepts: (A) ambient normoxia at sea level in the contemporary atmosphere and corresponding dissolved O2 concentration at air saturation of aqueous environments; (B) biological compartmental O2 levels at ambient normoxia under physiological activity of healthy organisms in the absence of environmental stress (e.g. in a diving human, a stranded whale, a thermally stressed animal); and (C) O2 levels above the control region, i.e., where the capacity for O2 consumption is not compromised by partial O2 pressure as evaluated by its kinetics. Conversely, the abc of hypoxia is concerned with deviations from these reference points caused by different mechanisms: (a) ambient alterations of oxygen levels; (b) biological O2 demand exceeding O2 supply under pathological or experimental limitations of convective O2 transport or O2 diffusion; and (c) critical oxygen pressure in oxygen kinetics shifted by pathological and toxicological effects or environmental stress. The ABC of hypoxia may be of help in the design and interpretation of in vitro and in vivo experimental studies.
• Keywords: ambient, anoxia, critical O2 pressure pc, functional hypoxia, hyperoxia, hypoxia, limiting O2 pressure pl, normoxia, oxygen O2, O2 concentration cO2 [µM], O2 pressure pO2 [kPa] • Bioblast editor: Gnaiger E • O2k-Network Lab: AT Innsbruck Oroboros, HU Budapest Tretter L, CH Lausanne Place N
Authors
- 1 Oroboros Instruments, Innsbruck, Austria
- 2 Institute of Sport Sciences, Univ. Lausanne, Switzerland
- 3 Department of Medical Biochemistry, Semmelweis University, Budapest, HU
- * Corresponding author: [email protected]
- Acknowledgements
- We thank Martin Burtscher for making us aware of the ABC of oxygen, Adam Chicco for critical comments on absolute versus evolutionary definitions of normoxia, and Malcolm J Shick and Adalberto L Val for discussions. Chris Donnelly was supported by the Swiss National Science Foundation under grant agreement nº 194964.
- Acknowledgements
Correction of errors
- Figure 1: Instead of "1 kPa = 0.133322 mmHg", the correct conversion is: "1 mmHg = 0.133322 kPa".
- Section 2.5: Instead of "At ambient normoxia, the concentration of O2 in dry air at 25 °C equals ΦO2·(RT)-1 = 0.20946·(100-3.17) kPa·(2.479 kJ·mol-1)-1 = 8.18 mM", these values refer to humid (water-vapour saturated) air, and the correct relation is: ΦO2·(pb-pH2O*)·(RT)-1 = 0.20946·(100-3.17) kPa·(2.479 kJ·mol-1)-1 = 8.18 mM.
On definitions
- Definitions always leak at the margins, where experts delight in posing counterexamples for their peers to ponder. Fortunately, the typical cases are clear enough that a little fuzziness around the edges does not interfere with the larger picture (Miller 1991 Scientific American Library).
- A lexicographer tries, not always successfully, to steer a course between incomprehension and miscomprehension. .. writing definitions is a difficult and little-appreciated art (Miller 1991 Scientific American Library).
- Full standardisation of definitions and analytical procedures could be feasible for new research efforts. .. For existing datasets and studies, harmonisation attempts to achieve some, but not necessarily perfect, homogeneity of definitions might need substantial effort and coordination. .. Large consortia and collaborations can allow the use of a common language among investigators for clinical definitions, laboratory measurements, and statistical analyses (Ioannidis 2014 Lancet).
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Keywords: Oxia terms
- Bioblast links: Hypoxia, normoxia, hyperoxia - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
| Term | Abbreviation | Description |
|---|---|---|
| Aerobic | ox | The aerobic state of metabolism is defined by the presence of oxygen (air) and therefore the potential for oxidative reactions (ox) to proceed, particularly in oxidative phosphorylation (OXPHOS). Aerobic metabolism (with involvement of oxygen) is contrasted with anaerobic metabolism (without involvement of oxygen): Whereas anaerobic metabolism may proceed in the absence or presence of oxygen (anoxic or oxic conditions), aerobic metabolism is restricted to oxic conditions. Below the critical oxygen pressure, aerobic ATP production decreases. |
| Anaerobic | Anaerobic metabolism takes place without the use of molecular oxygen, in contrast to aerobic metabolism. The capacity for energy assimilation and growth under anoxic conditions is the ultimate criterion for facultative anaerobiosis. Anaerobic metabolism may proceed not only under anoxic conditions or states, but also under hyperoxic and normoxic conditions (aerobic glycolysis), and under hypoxic and microxic conditions below the limiting oxygen pressure. | |
| Anoxia | anox | Ideally the terms anoxia and anoxic (anox, without oxygen) should be restricted to conditions where molecular oxygen is strictly absent. Practically, effective anoxia is obtained when a further decrease of experimental oxygen levels does not elicit any physiological or biochemical response. The practical definition, therefore, depends on (i) the techiques applied for oxygen removal and minimizing oxygen diffusion into the experimental system, (ii) the sensitivity and limit of detection of analytical methods of measuring oxygen (O2 concentration in the nM range), and (iii) the types of diagnostic tests applied to evaluate effects of trace amounts of oxygen on physiological and biochemical processes. The difficulties involved in defining an absolute limit between anoxic and microxic conditions are best illustrated by a logarithmic scale of oxygen pressure or oxygen concentration. In the anoxic state (State 5), any aerobic type of metabolism cannot take place, whereas anaerobic metabolism may proceed under oxic or anoxic conditions. |
| Critical oxygen pressure | pc | The critical oxygen pressure, pc, is defined as the partial oxygen pressure, pO2, below which aerobic catabolism (respiration or oxygen consumption) declines significantly. If anaerobic catabolism is activated simultaneously to compensate for lower aerobic ATP generation, then the limiting oxygen pressure, pl, is equal to the pc. In many cases, however, the pl is substantially lower than the pc. |
| Hyperoxia | hyperox | Hyperoxia is defined as environmental oxygen pressure above the normoxic reference level. Cellular and intracellular hyperoxia is imposed on isolated cells and isolated mitochondria at air-level oxygen pressures which are higher compared to cellular and intracellular oxygen pressures under tissue conditions in vivo. Hyperoxic conditions may impose oxidative stress and may increase maximum aerobic performance. |
| Hypoxia | hypox | Hypoxia (hypox) is defined in respiratory physiology as the state when insufficient O2 is available for respiration, compared to environmental hypoxia defined as environmental oxygen pressures below the normoxic reference level. Three major categories of hypoxia are (1) environmental hypoxia, (2) physiological tissue hypoxia in hyperactivated states (e.g. at VO2max) with intracellular oxygen demand/supply balance at steady state in tissues at environmental normoxia, compared to tissue normoxia in physiologically balanced states, and (3) pathological tissue hypoxia including ischemia and stroke, anaemia, chronic heart disease, chronic obstructive pulmonary disease, severe COVID-19, and obstructive sleep apnea. Pathological hypoxia leads to tissue hypoxia and heterogenous intracellular anoxia. Clinical oxygen treatment ('environmental hyperoxia') may not or only partially overcome pathological tissue hypoxia. |
| Intracellular oxygen | pO2,i | Physiological, intracellular oxygen pressure is significantly lower than air saturation under normoxia, hence respiratory measurements carried out at air saturation are effectively hyperoxic for cultured cells and isolated mitochondria. |
| Limiting oxygen pressure | pl | The limiting oxygen pressure, pl, is defined as the partial oxygen pressure, pO2, below which anaerobic catabolism is activated to contribute to total ATP generation. The limiting oxygen pressure, pl, may be substantially lower than the critical oxygen pressure, pc, below which aerobic catabolism (respiration or oxygen consumption) declines significantly. |
| Microxia | microx | Microxia (deep hypoxia) is obtained when trace amounts of O2 exert a stimulatory effect on respiration above the level where metabolism is switched to a purely anaerobic mode. |
| Normoxia | normox |  |
- General
- Related keyword lists
Publications: Tissue normoxia
| Year | Reference | Organism | Tissue;cell | Preparations | Stress | Diseases | |
|---|---|---|---|---|---|---|---|
| Donnelly 2022 BEC | 2022 | Donnelly C, Schmitt S, Cecatto C, Cardoso LHD, Komlódi T, Place N, Kayser B, Gnaiger E (2022) The ABC of hypoxia – what is the norm. Bioenerg Commun 2022.12.v2. https://doi.org/10.26124/bec:2022-0012.v2 | Oxidative stress;RONS Hypoxia | ||||
| Donnelly 2022 MitoFit Hypoxia | 2022 | Donnelly C, Schmitt S, Cecatto C, Cardoso LHD, Komlodi T, Place N, Kayser B, Gnaiger E (2022) The ABC of hypoxia – what is the norm. https://doi.org/10.26124/mitofit:2022-0025.v2 — 2022-11-14 published in Bioenerg Commun 2022.12. | Oxidative stress;RONS Hypoxia | ||||
| DiProspero 2021 Toxicol In Vitro | 2021 | DiProspero TJ, Dalrymple E, Lockett MR (2021) Physiologically relevant oxygen tensions differentially regulate hepatotoxic responses in HepG2 cells. https://doi.org/10.1016/j.tiv.2021.105156 | Liver | Intact cells | Hypoxia | ||
| Stepanova 2020 Methods Cell Biol | 2020 | Stepanova A, Galkin A (2020) Measurement of mitochondrial H2O2 production under varying O2 tensions. https://doi.org/10.1016/bs.mcb.2019.12.008 | Mouse | Nervous system | Isolated mitochondria | Oxidative stress;RONS | |
| Keeley 2019 Physiol Rev | 2019 | Keeley TP, Mann GE (2019) Defining physiological normoxia for improved translation of cell physiology to animal models and humans. https://doi.org/10.1152/physrev.00041.2017 | |||||
| Ast 2019 Nat Metab | 2019 | Ast T, Mootha VK (2019) Oxygen and mammalian cell culture: are we repeating the experiment of Dr. Ox? Nat Metab 1:858-860. | |||||
| Stepanova 2018 J Neurochem | 2018 | Stepanova A, Konrad C, Manfredi G, Springett R, Ten V, Galkin A (2018) The dependence of brain mitochondria reactive oxygen species production on oxygen level is linear, except when inhibited by antimycin A. J Neurochem 148:731-45. | Mouse | Nervous system | Isolated mitochondria | Ischemia-reperfusion Oxidative stress;RONS | |
| Stuart 2018 Oxid Med Cell Longev | 2018 | Stuart JA, Fonseca JF, Moradi F, Cunningham C, Seliman B, Worsfold CR, Dolan S, Abando J, Maddalena LA (2018) How Supraphysiological Oxygen Levels in Standard Cell Culture Affect Oxygen-Consuming Reactions. Oxid Med Cell Longev 2018:8238459. | |||||
| Stepanova 2018 J Cereb Blood Flow Metab | 2018 | Stepanova A, Konrad C, Guerrero-Castillo S, Manfredi G, Vannucci S, Arnold S, Galkin A (2018) Deactivation of mitochondrial complex I after hypoxia-ischemia in the immature brain. J Cereb Blood Flow Metab 39:1790-802. | Rat | Nervous system | Isolated mitochondria | Hypoxia Ischemia-reperfusion | |
| Stepanova 2017 J Cereb Blood Flow Metab | 2017 | Stepanova A, Kahl A, Konrad C, Ten V, Starkov AS, Galkin A (2017) Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia-reperfusion injury. J Cereb Blood Flow Metab 37:3649-58. | Mouse | Nervous system | Isolated mitochondria | Ischemia-reperfusion | |
| Harrison 2015 J Appl Physiol | 2015 | Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E (2015) Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol 119:1210-8. https://doi.org/10.1152/japplphysiol.00146.2015 | Mouse Bovines | Heart | Isolated mitochondria | Hypoxia | |
| Carreau 2011 J Cell Mol Med | 2011 | Carreau A, El Hafny-Rahbi B, Matejuk A, Grillon C, Kieda C (2011) Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. https://doi.org/10.1111/j.1582-4934.2011.01258.x | |||||
| Richardson 2006 J Physiol | 2006 | Richardson RS, Duteil S, Wary C, Wray DW, Hoff J, Carlier PG (2006) Human skeletal muscle intracellular oxygenation: the impact of ambient oxygen availability. https://doi.org/10.1113/jphysiol.2005.102327 | Human | Skeletal muscle | Hypoxia | ||
| Pettersen 2005 Cell Prolif | 2005 | Pettersen EO, Larsen LH, Ramsing NB, Ebbesen P (2005) Pericellular oxygen depletion during ordinary tissue culturing, measured with oxygen microsensors. Cell Prolif 38:257-67. | |||||
| Gnaiger 2003 Adv Exp Med Biol | 2003 | Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. https://doi.org/10.1007/978-1-4419-8997-0_4 | Human Rat | Heart Liver Endothelial;epithelial;mesothelial cell Fibroblast | Intact cells Permeabilized cells Permeabilized tissue Isolated mitochondria Oxidase;biochemical oxidation | ||
| Gnaiger 2001 Respir Physiol | 2001 | Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. https://doi.org/10.1016/S0034-5687(01)00307-3 | Human Rat | Heart Liver Endothelial;epithelial;mesothelial cell HUVEC | Intact cells Isolated mitochondria | Oxidative stress;RONS | |
| Gnaiger 2000 Proc Natl Acad Sci U S A | 2000 | Gnaiger E, Méndez G, Hand SC (2000) High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci U S A 97:11080-5. https://doi.org/10.1073/pnas.97.20.11080 | Rat Artemia Crustaceans | Liver | Isolated mitochondria | ||
| Gnaiger 1998 J Exp Biol | 1998 | Gnaiger E, Lassnig B, Kuznetsov AV, Rieger G, Margreiter R (1998) Mitochondrial oxygen affinity, respiratory flux control, and excess capacity of cytochrome c oxidase. https://doi.org/10.1242/jeb.201.8.1129 | Human Rat | Heart Liver Endothelial;epithelial;mesothelial cell HUVEC | Isolated mitochondria Enzyme Oxidase;biochemical oxidation Intact cells | ||
| Gnaiger 1998 Biochim Biophys Acta | 1998 | Gnaiger E, Lassnig B, Kuznetsov AV, Margreiter R (1998) Mitochondrial respiration in the low oxygen environment of the cell: Effect of ADP on oxygen kinetics. Biochim Biophys Acta 1365:249-54. https://doi.org/10.1016/S0005-2728(98)00076-0 | Rat | Heart Liver | Isolated mitochondria | ||
| Gnaiger 1995 J Bioenerg Biomembr | 1995 | Gnaiger E, Steinlechner-Maran R, Méndez G, Eberl T, Margreiter R (1995) Control of mitochondrial and cellular respiration by oxygen. https://doi.org/10.1007/BF02111656 | Human Rat | Liver Endothelial;epithelial;mesothelial cell HUVEC | Isolated mitochondria Intact cells | ||
| Gnaiger 1993 Transitions | 1993 | Gnaiger E (1993) Homeostatic and microxic regulation of respiration in transitions to anaerobic metabolism. In: The vertebrate gas transport cascade: Adaptations to environment and mode of life. Bicudo JEPW (ed), CRC Press, Boca Raton, Ann Arbor, London, Tokyo:358-70. | Reptiles Fishes Crustaceans Annelids | Intact organism | |||
| Gnaiger 1991 Soc Exp Biol Seminar Series | 1991 | Gnaiger E (1991) Animal energetics at very low oxygen: Information from calorimetry and respirometry. In: Strategies for gas exchange and metabolism. Woakes R, Grieshaber M, Bridges CR (eds), Soc Exp Biol Seminar Series 44, Cambridge Univ Press, London:149-71. | Annelids | Intact organism | |||
| Gnaiger 1983 J Exp Zool | 1983 | Gnaiger E (1983) Heat dissipation and energetic efficiency in animal anoxibiosis. Economy contra power. J Exp Zool 228:471-90. | Annelids Molluscs | Skeletal muscle | Intact organism |
- Abstracts: Tissue normoxia
| Year | Reference | Organism | Tissue;cell | Preparations | Stress | Diseases | |
|---|---|---|---|---|---|---|---|
| Donnelly 2022 Abstract Bioblast | 2022 | 2.1. «10+5»  »MitoFit Preprint« | Oxidative stress;RONS Hypoxia | ||||
| Gnaiger 2018 AussieMit | 2018 | Komlodi Timea, Sobotka Ondrej, Doerrier Carolina, Gnaiger Erich (2018) Mitochondrial H2O2 production is low under tissue normoxia but high at in-vitro air-level oxygen pressure - comparison of LEAK and OXPHOS states. AussieMit 2018 Melbourne AU. | Mouse Saccharomyces cerevisiae | Heart Nervous system | Isolated mitochondria Intact cells | Oxidative stress;RONS Hypoxia | |
| Sobotka 2018 MiP2018 | 2018 |  | Mouse Saccharomyces cerevisiae | Heart Nervous system | Isolated mitochondria | Hypoxia | |
| Komlodi 2017 MiP2017 | 2017 |  | Mouse | Heart Nervous system | Isolated mitochondria | Oxidative stress;RONS Hypoxia |
Labels: MiParea: Respiration, Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style
Stress:Oxidative stress;RONS, Hypoxia
Regulation: Aerobic glycolysis, Flux control, Temperature
Coupling state: ROUTINE
HRR: Oxygraph-2k
Tissue normoxia
