Control of mitochondrial and cellular respiration by oxygen

Control and regulation of mitochondrial and cellular respiration by oxygen is discussed with three aims: (1) A review of intracellular oxygen levels and gradients, particularly in heart, emphasizes the dominance of extracellular oxygen gradients. Intracellular oxygen pressure,\(p_{O_2 } \), is low, typically one to two orders of magnitude below incubation conditions used routinely for the study of respiratory control in isolated mitochondria. The\(p_{O_2 } \) range of respiratory control by oxygen overlaps with cellular oxygen profiles, indicating the significance of\(p_{O_2 } \) in actual metabolic regulation. (2) A methodologically detailed discussion of high-resolution respirometry is necessary for the controversial topic of respiratory control by oxygen, since the risk of methodological artefact is closely connected with far-reaching theoretical implications. Instrumental and analytical errors may mask effects of energetic state and partially explain the divergent views on the regulatory role of intracellular\(p_{O_2 } \). Oxygen pressure for half-maximum respiration,p₅₀, in isolated mitochondria at state 4 was 0.025 kPa (0.2 Torr; 0.3 ΜM O₂), whereasp₅₀ in endothelial cells was 0.06–0.08 kPa (0.5 Torr). (3) A model derived from the thermodynamics of irreversible processes was developed which quantitatively accounts for near-hyperbolic flux/\(p_{O_2 } \) relations in isolated mitochondria. The apparentp₅₀ is a function of redox potential and protonmotive force. The protonmotive force collapses after uncoupling and consequently causes a decrease inp₅₀. Whereas it is becoming accepted that flux control is shared by several enzymes, insufficient attention is paid to the notion of complementary kinetic and thermodynamic flux control mechanisms.