The modulation of thiol redox state affects the production and metabolism of hydrogen peroxide by heart mitochondria

In rat heart mitochondria, auranofin, arsenite, diamide, and BCNU increase H2O2 formation, further stimulated by antimycin. However, in submitochondrial particles, H2O2 formation and oxygen uptake are not affected, indicating that these substances do not alter respiration. Mitochondria are also able to rapidly metabolize added H2O2, in a process partially prevented by BCNU or auranofin. Calcium does not modify the production or H2O2 and the mitochondrial thioredoxin system is not affected by calcium ions. Auranofin, arsenite, and diamide determine a large mitochondrial permeability transition. while BCNU and acetoacetate are ineffective. Thiols and glutathione are modified only by BCNU and diamide. However, all the compounds tested cause the release of cytochrome c that occurs also in the absence of mitochondrial swelling. In conclusion, the compounds utilized share the common feature of shifting the mitoclondrial thiol-linked redox balance towards a more oxidized condition that is responsible of the observed effects. (c) 2005 Elsevier Inc. All rights reserved.