CONTROL OF MITOCHONDRIAL AND CELLULAR RESPIRATION BY OXYGEN

Control and regulation of mitochondrial and cellular respiration by ox ygen is discussed with three aims: (1) A review of intracellular oxyge n levels and gradients, particularly in heart, emphasizes the dominanc e of extracellular oxygen gradients. Intracellular oxygen pressure, p( O2) is low, typically one to two orders of magnitude below incubation conditions used routinely for the study of respiratory control in isol ated mitochondria. The p(O2) range of respiratory control by oxygen ov erlaps with cellular oxygen profiles, indicating the significance of p (O2) in actual metabolic regulation. (2) A methodologically detailed d iscussion of high-resolution respirometry is necessary for the controv ersial topic of respiratory control by oxygen, since the risk of metho dological artefact is closely connected with far-reaching theoretical implications. Instrumental and analytical errors may mask effects of e nergetic state and partially explain the divergent views on the regula tory role of intracellular p(O2). Oxygen pressure for half-maximum res piration, p(50), in isolated mitochondria at state 4 was 0.025 kPa (0. 2 Torr; 0.3 mu M O-2), whereas p(50) in endothelial cells was 0.06-0.0 8 kPa (0.5 Torr). (3) A model derived from the thermodynamics of irrev ersible processes was developed which quantitatively accounts for near -hyperbolic flux/p(O2) relations in isolated mitochondria. The apparen t p(50) is a function of redox potential and protonmotive force. The p rotonmotive force collapses after uncoupling and consequently causes a decrease in p(50). Whereas it is becoming accepted that flux control is shared by several enzymes, insufficient attention is paid to the no tion of complementary kinetic and thermodynamic flux control mechanism s.