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 (ΔpH), were measured on mitochondrial H2O2 release. As expected, Pi decreased ΔpH and increased the electric membrane potential (ΔΨ). 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.