Gnaiger 1991 Soc Exp Biol Seminar Series
|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.|
Abstract: A previous critique of the term facultative invertebrate anaerobiosis focused on the duration of anoxia. An addition, important, yet much neglected aspect is dicussed here, namely the extent and quantification of the 'anaerobic' condition. • Keywords: CaloRespirometry, Twin-Flow
- Still, mammalian biochemists are insufficiently aware of the importance of anaerobic mitochondrial energy transformation in metazoans, although ATP formation coupled to anaerobic mitochondrial electron transport occurs not only in invertebrates (Saz, 1981) but in mammalian myocyte mitochondria (Wiesner et al., 1988).
- In zoophysiology, 'anaerobic' (without air) is rarely defined in terms of controlled measurements of the actual extent of anaerobic conditions.
- Metabolic hypoxia is indicated as a reduced oxygen flux below the critical oxygen pressure (Figure 2) and is either fully or partially anaerobic.
- In a perfect conformer the relation between oxygen flux and pressure is not only linear but proportional (for a discussion of generalized flux-pressure relations, see Gnaiger (1989)).
- Microxic regulation .. effectively increases the slope of the flux-pressure relation in the microxic region.
- The slope of an ideal conformer is equivalent to a 5 % increase of oxygen flux per kPa (Figure 5a).
- Below the critical oxygen pressure, the aerobic ATP production decreases, and below the limiting oxygen pressure anaerobic processes compensate increasingly for the diminished aerobic flux.
- Microxic regulation enables a steep increase of oxygen flux with pO2 at very low oxygen levels. This is a metabolic adaptation to environments in the boundary to anoxic conditions, offering an energetic advantage to active organisms.
- The difficulties involved in defining an absolute limit between microxic and anoxic conditions are best illustrated by a logarithmic pO2 scale (Figure 7). Ideally the term 'anoxic' (without oxygen) should be restricted to any situation when molecular oxygen is strictly absent. Absence of oxygen, however, has to be practically defined in terms of tested oxygen removal techniques and relative to the sensitivity limit of analytical methods (Figure 7).
- The capacity for energy assimilation and growth under anoxia should be considered as the ultimate criterion for 'facultatively anaerobic' animals.
Keywords: Oxia terms
- Bioblast links: Hypoxia, normoxia, hyperoxia - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
|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||hypoxic compared to tissue normoxia when grown in ambient normoxia (95 % air and 5 % CO2) and a high layer of culture medium causing oxygen diffusion limitation at high respiratory activity, but pericellular pO2 may be effectively hyperoxic in cells with low respiratory rate with a thin layer of culture medium (<2 mm). Intracellular oxygen levels in well-stirred suspended small cells (5 - 7 mm diameter; endothelial cells, fibroblasts) are close to ambient pO2 of the incubation medium, such that matching the experimental intracellular pO2 to the level of intracellular tissue normoxia requires lowering the ambient pO2 of the medium to avoid hyperoxia.|
Publications: Tissue normoxia
|Donnelly 2022 MitoFit Hypoxia||2022-07-15||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 ||Oxidative stress;RONS|
|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|
|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|
|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 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. https://doi.org/10.1152/japplphysiol.00146.2015||Mouse|
|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|
|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|
|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. https://doi.org/10.1073/pnas.97.20.11080||Rat|
|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|
|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.||Rat||Heart|
|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. J Bioenerg Biomembr 27:583-96.||Human|
|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|
|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|
|Skeletal muscle||Intact organism|
- Abstracts: Tissue normoxia
|Donnelly 2022 Abstract Bioblast||2022||2.1. «10+5» https://doi.org/10.26124/bec:2022-0001 |
|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|
|Sobotka 2018 MiP2018||2018||Mouse|
|Komlodi 2017 MiP2017||2017||Mouse||Heart|
|Isolated mitochondria||Oxidative stress;RONS|
Labels: MiParea: Respiration, Instruments;methods, Comparative MiP;environmental MiP
Preparation: Intact organism
Regulation: Aerobic glycolysis, Oxygen kinetics, Substrate, Fatty acid, Amino acid Coupling state: ROUTINE
CaloRespirometry, Tissue normoxia, Twin-Flow, MitoFit2022rTCA, MitoFit2022Hypoxia