부산대학교 도서관

Mitochondrial reactive oxygen species (ROS) metabolism is unique in that mitochondria both generate and scavenge ROS. Recent estimates of ROS scavenging capacity of brain mitochondria are surprisingly high, ca. 9-12 nmol HO/min/mg, which is ~100 times higher than the rate of ROS generation. This raises a question whether brain mitochondria are a source or a sink of ROS. We studied the interaction between ROS generation and scavenging in mouse brain mitochondria by measuring the rate of removal of HO added at a concentration of 0.4 μM, which is close to the reported physiological HO concentrations in tissues, under conditions of low and high levels of mitochondrial HO generation. With NAD-linked substrates, the rate of HO generation by mitochondria was ~50-70 pmol/min/mg. The HO scavenging dynamics was best approximated by the first order reaction equation. HO scavenging was not affected by the uncoupling of mitochondria, phosphorylation of added ADP, or the genetic ablation of glutathione peroxidase 1, but decreased in the absence of respiratory substrates, in the presence of thioredoxin reductase inhibitor auranofin, or in partially disrupted mitochondria. With succinate, the rate of HO generation was ~2,200-2,900 pmol/min/mg; the scavenging of added HO was masked by a significant accumulation of generated HO in the assay medium. The obtained data were fitted into a simple model that reasonably well described the interaction between HO scavenging and production. It showed that mitochondria are neither a sink nor a source of HO, but can function as both at the same time, efficiently stabilizing exogenous HO concentration at a level directly proportional to the ratio of the HO generation rate to the rate constant of the first order scavenging reaction. [ABSTRACT FROM AUTHOR]