Gnaiger 1998 J Exp Biol
|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|
Abstract: The oxygen affinity of the enzyme system involved in mitochondrial respiration indicates, in relation to intracellular oxygen levels and interpreted with the aid of flux control analysis, a significant role of oxygen supply in limiting maximum exercise. This implies that the flux control coefficient of mitochondria is not excessively high, based on a capacity of mitochondrial oxygen consumption that is slightly higher than the capacity for oxygen supply through the respiratory cascade. Close matching of the capacities and distribution of flux control is consistent with the concept of symmorphosis. Within the Electron transfer-pathway (respiratory chain), however, the large excess capacity of cytochrome c oxidase, COX, appears to be inconsistent with the economic design of the respiratory cascade. To address this apparent discrepancy, we used three model systems: cultured endothelial cells and mitochondria isolated from heart and liver. Intracellular oxygen gradients increase with oxygen flux, explaining part of the observed decrease in oxygen affinity with increasing metabolic rate in cells. In addition, mitochondrial oxygen affinities decrease from the resting to the active state. The oxygen affinity in the active ADP-stimulated state is higher in mitochondria from heart than in those from liver, in direct relationship to the higher excess capacity of COX in heart. This yields, in turn, a lower turnover rate of COX even at maximum flux through the Electron transfer-pathway, which is necessary to prevent a large decrease in oxygen affinity in the active state. Upregulation of oxygen affinity provides a functional explanation of the excess capacity of COX. The concept of symmorphosis, a matching of capacities in the respiratory cascade, is therefore complemented by ‘synkinetic’ considerations on optimum enzyme ratios in the eöectron transfer system. Accordingly, enzymatic capacities are matched in terms of optimum ratios, rather than equal levels, to meet the specific kinetic and thermodynamic demands set by the low-oxygen environment in the cell. • Keywords: Oxygen flux, Catalytic efficiency, Hypoxia, Respiratory cascade, Respiratory chain, Flux control analysis, Endothelial cell, Liver, Heart, Mitochondria
• O2k-Network Lab: AT Innsbruck Gnaiger E
- State 2 in this publication (different from definitions by Chance, Williams 1955) has the meaning of a LEAK state of respiration, without added adenylates (no ADP and no ATP) in the presence of defined respiratory carbon substrates.
- State 4 in this publication is a LEAK state of respiration induced by addition of defined respiratory carbon substrates and a high concenteration of ATP.
- State 3 in this publication is measured at high [ADP] close to saturated [ADP] (OXPHOS capacity) in the presence of added ATP.
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, Comparative MiP;environmental MiP
Organism: Human, Rat Tissue;cell: Heart, Liver, Endothelial;epithelial;mesothelial cell, HUVEC Preparation: Isolated mitochondria, Enzyme, Oxidase;biochemical oxidation, Intact cells
Regulation: Flux control, Oxygen kinetics, Substrate, Threshold;excess capacity Coupling state: ROUTINE, OXPHOS Pathway: N, S, CIV HRR: Oxygraph-2k
Tissue normoxia, BEC 2020.2, MitoFit2022Hypoxia