Difference between revisions of "Gnaiger 2000 Proc Natl Acad Sci U S A"
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|journal=Proc Natl Acad Sci U S A | |journal=Proc Natl Acad Sci U S A | ||
|abstract=Mitochondria are confronted with low oxygen levels in the microenvironment within tissues; yet, isolated mitochondria are routinely studied under air-saturated conditions that are effectively hyperoxic, increase oxidative stress, and may impair mitochondrial function. Under hypoxia, on the other hand, respiration and ATP supply are restricted. Under these conditions of oxygen limitation, any compromise in the coupling of oxidative phosphorylation to oxygen consumption could accentuate ATP depletion, leading to metabolic failure. To address this issue, we have developed the approach of oxygen-injection microcalorimetry and ADP-injection respirometry for evaluating mitochondrial function at limiting oxygen supply. Whereas phosphorylation efficiency drops during ADP limitation at high oxygen levels, we show here that oxidative phosphorylation is more efficient at low oxygen than at air saturation, as indicated by higher ratios of ADP flux to total oxygen flux at identical submaximal rates of ATP synthesis. At low oxygen, the proton leak and uncoupled respiration are depressed, thus reducing maintenance energy expenditure. This indicates the importance of low intracellular oxygen levels in avoiding oxidative stress and protecting bioenergetic efficiency. | |abstract=Mitochondria are confronted with low oxygen levels in the microenvironment within tissues; yet, isolated mitochondria are routinely studied under air-saturated conditions that are effectively hyperoxic, increase oxidative stress, and may impair mitochondrial function. Under hypoxia, on the other hand, respiration and ATP supply are restricted. Under these conditions of oxygen limitation, any compromise in the coupling of oxidative phosphorylation to oxygen consumption could accentuate ATP depletion, leading to metabolic failure. To address this issue, we have developed the approach of oxygen-injection microcalorimetry and ADP-injection respirometry for evaluating mitochondrial function at limiting oxygen supply. Whereas phosphorylation efficiency drops during ADP limitation at high oxygen levels, we show here that oxidative phosphorylation is more efficient at low oxygen than at air saturation, as indicated by higher ratios of ADP flux to total oxygen flux at identical submaximal rates of ATP synthesis. At low oxygen, the proton leak and uncoupled respiration are depressed, thus reducing maintenance energy expenditure. This indicates the importance of low intracellular oxygen levels in avoiding oxidative stress and protecting bioenergetic efficiency. | ||
|mipnetlab=AT Innsbruck Gnaiger E, US LA Baton Rouge Hand SC | |mipnetlab=AT Innsbruck Oroboros, AT Innsbruck Gnaiger E, US LA Baton Rouge Hand SC | ||
}} | }} | ||
== Selected quotes == | |||
::::* Atmospheric oxygen levels were probably 0.1 % of the present when mitochondria became associated with cells early during evolution (1-4). Such low-oxygen conditions persist in extreme environments (5-8), and oxygen pessures as low as 0.3-0.4 kPa (2-3 mmHg) are observed in the intracellular microenvironment of mitochondria in tissues under [[normoxic |normoxia]] (9-13). Even so, in typical studies with isolated mitochondria, these organelles are artificially exposed to the high partial pressure of oxygen at air saturation (c. 20 kPa), despite the fact that this condition is effectively [[hyperoxic]], rarely physiological and increases oxidative stress (14, 15). | |||
::::* From the present study, it can be inferred that air-saturation as a reference condition is questionable for evaluating mitochondrial efficiency. If representative measures of performance are to be obtained for mitochondria and even cultured cells (42, 44), then oxygen tension should be shifted away from these non-physiological levels to minimize the risk of oxidative stress. | |||
::::* Furthermore, the high efficiency of oxidative phosphorylation at low oxygen emphasizes that even trace amounts of oxygen can make a vital energetic contribution when ATP limitation threatens cellular survival under severe hypoxia encountered at high altitude, in aquatic habitats, and during pathological states of ischemia. | |||
== Further details == | == Further details == | ||
:::* Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - [[Gnaiger 2001 Respir Physiol |»Bioblast link«]] | :::* Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - [[Gnaiger 2001 Respir Physiol |»Bioblast link«]] | ||
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|pathways=S | |pathways=S | ||
|instruments=Oxygraph-2k, TIP2k | |instruments=Oxygraph-2k, TIP2k | ||
|additional=Tissue normoxia, ATP, Steady state, BEC 2020.1, BEC 2020.2, MitoFit 2021 MgG | |additional=Tissue normoxia, ATP, Steady state, | ||
BEC 2020.1, BEC 2020.2, MitoFit 2021 MgG | |||
}} | }} | ||
Revision as of 21:38, 5 October 2021
| 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. |
Gnaiger Erich, Mendez Gabriela, Hand Steven C (2000) Proc Natl Acad Sci U S A
Abstract: Mitochondria are confronted with low oxygen levels in the microenvironment within tissues; yet, isolated mitochondria are routinely studied under air-saturated conditions that are effectively hyperoxic, increase oxidative stress, and may impair mitochondrial function. Under hypoxia, on the other hand, respiration and ATP supply are restricted. Under these conditions of oxygen limitation, any compromise in the coupling of oxidative phosphorylation to oxygen consumption could accentuate ATP depletion, leading to metabolic failure. To address this issue, we have developed the approach of oxygen-injection microcalorimetry and ADP-injection respirometry for evaluating mitochondrial function at limiting oxygen supply. Whereas phosphorylation efficiency drops during ADP limitation at high oxygen levels, we show here that oxidative phosphorylation is more efficient at low oxygen than at air saturation, as indicated by higher ratios of ADP flux to total oxygen flux at identical submaximal rates of ATP synthesis. At low oxygen, the proton leak and uncoupled respiration are depressed, thus reducing maintenance energy expenditure. This indicates the importance of low intracellular oxygen levels in avoiding oxidative stress and protecting bioenergetic efficiency.
• O2k-Network Lab: AT Innsbruck Oroboros, AT Innsbruck Gnaiger E, US LA Baton Rouge Hand SC
Selected quotes
- Atmospheric oxygen levels were probably 0.1 % of the present when mitochondria became associated with cells early during evolution (1-4). Such low-oxygen conditions persist in extreme environments (5-8), and oxygen pessures as low as 0.3-0.4 kPa (2-3 mmHg) are observed in the intracellular microenvironment of mitochondria in tissues under normoxia (9-13). Even so, in typical studies with isolated mitochondria, these organelles are artificially exposed to the high partial pressure of oxygen at air saturation (c. 20 kPa), despite the fact that this condition is effectively hyperoxic, rarely physiological and increases oxidative stress (14, 15).
- From the present study, it can be inferred that air-saturation as a reference condition is questionable for evaluating mitochondrial efficiency. If representative measures of performance are to be obtained for mitochondria and even cultured cells (42, 44), then oxygen tension should be shifted away from these non-physiological levels to minimize the risk of oxidative stress.
- Furthermore, the high efficiency of oxidative phosphorylation at low oxygen emphasizes that even trace amounts of oxygen can make a vital energetic contribution when ATP limitation threatens cellular survival under severe hypoxia encountered at high altitude, in aquatic habitats, and during pathological states of ischemia.
Further details
- 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«
Cited by
- 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
- Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002
- Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. doi:10.26124/bec:2020-0001.v1.
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, Comparative MiP;environmental MiP, Developmental biology
Organism: Rat, Artemia, Crustaceans
Tissue;cell: Liver
Preparation: Isolated mitochondria
Regulation: ADP, ATP, Coupling efficiency;uncoupling, Oxygen kinetics Coupling state: LEAK, OXPHOS Pathway: S HRR: Oxygraph-2k, TIP2k
Tissue normoxia, ATP, Steady state, BEC 2020.1, BEC 2020.2, MitoFit 2021 MgG
