Gnaiger 2003 Adv Exp Med Biol

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Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. Adv Exp Med Biol 543:39-55.

» PMID: 14713113, Bioblast pdf

Gnaiger E (2003) Adv Exp Med Biol

Abstract: Oxygen pressure declines from normoxic air-level to the microenvironment of mitochondria where cytochrome c oxidase (CIV) reduces oxygen to water at oxygen levels as low as 0.3 kPa (2 Torr; 3 μM; 1.5% air saturation). Intracellular hypoxia is defined as (1) local oxygen pressure below normoxic reference states, or (2) limitation of mitochondrial respiration by oxygen levels below kinetic saturation, resulting in oxyconformance. High-resolution respirometry provides the methodology to measure mitochondrial and cellular oxygen kinetics in the relevant low oxygen range <1 kPa (7.5 mmHg; 9-10 μM; 5% air saturation). Respiration of isolated heart mitochondria follows hyperbolic oxygen kinetics with half-saturating oxygen pressure, p50, of 0.04 kPa (0.3 Torr; 0.4 μM) in ADP-stimulated State 3. Thus mitochondrial respiration proceeds at 90% of its hyperbolic maximum at the p50 of myoglobin, suggesting the possibility of a small but significant oxygen limitation even under normoxia in active muscle. Any impairment of oxygen delivery, therefore, induces oxyconformance. In addition, a shift of mitochondrial oxygen kinetics to the right, particularly by competitive inhibition of CIV by NO, causes a further depression of respiration and a compensatory increase of local oxygen pressure. Above 1 kPa, mitochondrial oxygen uptake increases above hyperbolic saturation, which is probably due to oxygen radical production rather than the kinetics of CIV. In cultured cells, the pronounced oxygen uptake above mitochondrial saturation at air-level oxygen pressure cannot be inhibited by rotenone and antimycin A, amounting to >20% of ROUTINE respiration in fibroblasts. Biochemical models of oxyconformance of CIV are evaluated relative to patterns of intracellular oxygen distribution in the tissue and enzyme turnover in vivo, considering the kinetic effects of CIV excess capacity on flux through the mitochondrial electron transfer-pathway.

Keywords: Oxygen kinetics, Cytochrome c oxidase, Mitochondrial respiratory control, Oxygen limitation, Hypoxia

O2k-Network Lab: AT Innsbruck Gnaiger E


Labels: MiParea: Respiration 


Organism: Human, Rat  Tissue;cell: Heart, Liver, Endothelial;epithelial;mesothelial cell, Fibroblast  Preparation: Intact cells, Permeabilized cells, Permeabilized tissue, Isolated mitochondria, Oxidase;biochemical oxidation 

Regulation: Oxygen kinetics  Coupling state: ROUTINE, OXPHOS  Pathway: N, ROX  HRR: Oxygraph-2k