Gnaiger 2000 Proc Natl Acad Sci U S A

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Publications in the MiPMap
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.

» PMID: 11005877 Open Access

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 Gnaiger E, US LA Baton Rouge Hand SC


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:HRR: Oxygraph-2k, TIP2k 

Tissue normoxia, ATP, Steady state, BEC 2020.1, BEC 2020.2, MitoFit 2021 MgG, MitoFit 2021 Dark respiration, MitoFit 2021 Photosynthesis 

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«
» OXPHOS-coupling efficiency
» ETS coupling efficiency

Cited by

Gnaiger 2020 BEC MitoPathways


Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2:112 pp. doi:10.26124/bec:2020-0002
Gnaiger Erich et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1.


Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. doi:10.26124/bec:2020-0001.v1.


  • Cardoso et al (2021) Magnesium Green for fluorometric measurement of ATP production does not interfere with mitochondrial respiration. MitoFit Preprints 2021.1. doi:10.26124/mitofit:2021-0001
  • Huete-Ortega et al (2021) Substrate-uncoupler-inhibitor-titration protocols for dark respiration in Chlamydomonas reinhardtii. MitoFit Preprints 2021 (in prep).
  • Huete-Ortega et al (2021) Substrate-uncoupler-inhibitor-titration protocols for photosynthesis in Chlamydomonas reinhardtii. MitoFit Preprints 2021 (in prep).