Ammonium-dependent hydrogen peroxide production by mitochondria

NADH-supported generation of H2O2 by permeabilized rat heart mitochondria was partially prevented by the specific complex I-directed inhibitor, NADH-OH, and was significantly stimulated by ammonium. Ammonium did not affect H2O2 production by complex I in coupled submitochondrial particles. The soluble mitochondrial matrix protein fraction catalyzed NADH-dependent H2O2 production, which was greatly ( similar to 10fold) stimulated by ammonium. We conclude that complex I is not the major contributor to mitochondrial superoxide ( hydrogen peroxide) generation and that there are specific ammonium-sensitive NADH: oxygen oxidoreductase(s) in the mitochondrial matrix which are responsible for mitochondrial H2O2 production. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.