Phosphate Increases Mitochondrial Reactive Oxygen Species Release

Abstract

The effects of inorganic phosphate (Pi), the main intracellular membrane permeable anion capable of altering mitochondrial pH gradients (Delta pH), were measured on mitochondrial H2O2 release. As expected, Pi decreased Delta pH and increased the electric membrane potential (Delta Psi). Mitochondrial H2O2 release was stimulated by Pi and also by its structural analogue arsenate. However, acetate, another membrane-permeable anion, did not stimulate mitochondrial H2O2 release. The stimulatory effect promoted by Pi was prevented by CCCP, which decreases transport of Pi across the inner mitochondrial membrane, indicating that Pi must be in the mitochondrial matrix to stimulate H2O2 release. In conclusion, we found that Pi and arsenate stimulate mitochondrial reactive oxygen release, an effect that may contribute towards oxidative stress under conditions such as ischemia/reperfusion, in which high-energy phosphate bonds are hydrolyzed.

Integration of rapid cytosolic Ca2+signals by mitochondria in cat ventricular myocytes

“…P i is the main intracellular membranepermeant anion and enters the mitochondrial matrix together with protons. Mitochondrial P i uptake lowers mitochondrial pH and increases ⌬⌿ and therefore the electrical driving force for Ca 2ϩ uptake (10,40). Thus, through these mechanisms, it is expected that higher levels of P i would facilitate mitochondrial Ca 2ϩ uptake.…”

Normothermic Versus Hypothermic Ex Vivo Flush Using a Novel Phosphate-Free Preservation Solution (AQIX) in Porcine Kidneys

“…AQIX utilizes the NaHCO3/pCO2 buffer system in combination with Good's buffer BES rather than the traditional phosphate-buffered solutions, which are known to inhibit glycolysis and oxidative phosphorylation [13]. Inorganic phosphate has also been associated with the release of reactive oxygen species [14]. BES maintains a stable pH and has been shown to give superior metabolic effects in hypothermic preservation of porcine hearts with higher ATP levels, ATP:ADP ratios, and conservation of phosphofructokinase compared with other buffering agents when included in a modified UW solution [15].…”

Antioxidant activity of natural compounds of Stachytarpheta cayennensis (Rich.) Vahl, Verbenaceae, by scavenger of mitochondrial reactive oxygen species

“…This structural information could justify its high antioxidant activity when compared to the other compounds tested (Zhou & Sadik, 2008). Perhaps, the weak antioxidant activity of quercetin reported here may be related to the solubility and ability of quercetin to be distributed to a less or greater extent of its diffusion speed, between the lipid-water interface, or the distribution in the hydrophobic core of the mitochondrial membrane (Justino et al, 2004;Oliveira & Kowaltowski, 2004;Pulido et al, 2005;Spencer et al, 2004).…”

“…The formation of ROS is inevitable during normal oxidative metabolism, and it is well established that some of the oxygen (O 2 ) consumed by the ETS generate ROS, mostly at complexes I and III (Cadenas et al, 1977, Cadenas & Davies, 2000Chen et al, 2003;Boveris et al, 1976;Boveris & Chance, 1973;Turrens & Boveris, 1980). The partial reduction of molecular oxygen, during oxidative phosphorylation, leads to a constant flux of superoxide anion (O 2 -), the precursor of hydrogen peroxide (H 2 O 2 ) radicals (Liu, 2002;Oliveira & Kowaltowski, 2004). It has been described in the literature that in pathological conditions ROS production can be exacerbated, resulting in an imbalance between ROS generation and the intracellular levels of antioxidant defenses (Brand et al, 2004;Turrens 2003).…”