Control of mitochondrial and cellular respiration by oxygen

Abstract

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, pO2, is low, typically one to two orders of magnitude below incubation conditions used routinely for the study of respiratory control in isolated mitochondria. The pO2 range of respiratory control by oxygen overlaps with cellular oxygen profiles, indicating the significance of pO2 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 pO2. Oxygen pressure for half-maximum respiration, p50, in isolated mitochondria at state 4 was 0.025 kPa (0.2 Torr; 0.3 microM O2), whereas p50 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/pO2 relations in isolated mitochondria. The apparent p50 is a function of redox potential and protonmotive force. The protonmotive force collapses after uncoupling and consequently causes a decrease in p50. 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.

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

“…At low blood flow rates, this factor controls the sensitivity of oxygen consumption to depletion of mitochondrial oxygen at the prevailing cytochrome oxidase activity, as noted in previous reports of variable cytochrome oxidase affinity (Brown and Cooper 1994;Brown 1995;Gnaiger et al, 1995Gnaiger et al, , 1998Brown, 2001).…”

On the mechanism by which vascular endothelial cells regulate their oxygen consumption

“…Cumulative evidence indicates that a haem protein is involved (29), and cytochrome c oxidase has been proposed as a candidate (30,31). However, the K m (or p50) for oxygen observed in the isolated enzyme and mitochondrial preparations is 5-10ϫ lower than that measured in whole cells and tissues (32)(33)(34)(35)(36). Several hypotheses have been put forward to explain this discrepancy, such as the oxygen gradient across the plasma membrane, clustering of mitochondria, or changes in the concentrations of pyridine nucleotides (13,37).…”

Endocrine, biotransformation, and oxidative stress responses in salmon hepatocytes exposed to chemically induced hypoxia and perfluorooctane sulfonamide (PFOSA), given singly or in combination

“…Previously, the alteration of biotransformation and hormonal systems by hypoxia has been reported in both in vivo and in vitro studies (du Souich and Fradette 2011; Shang et al 2006;Wu et al 2003). In addition, hypoxia has been shown to produce cellular oxidative stress responses in several fish species (Clotfelter et al 2013;Gnaiger et al 1995;Mansfield et al 2005;Olsvik et al 2013). In the present study, our data show that transcript levels for endocrine (ERα, Vtg and Zrp), biotransformation (cyp1a, cyp3a, gst and udpgt) and oxidative stress (cat, gpx and gr) responses were differentially modulated by PFOSA and hypoxia alone or in combination, and these effects were mostly hypoxia-dependent and affected by exposure duration.…”

“…In mammalian systems, PFOSA is metabolically degraded to PFOS at a slow rate, but also undergoes enterohepatic circulation and mediate oxidative stress responses (Slotkin et al 2008;Xu et al 2004). Sustained hypoxia is known to cause oxidative stress, due to increased formation of ROS, produced by metabolism and the electron transport chain (Gnaiger et al 1995;Mansfield et al 2005;Nathan and Cunningham-Bussel 2013).…”