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2014 ; 46
(6
): 471-7
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Scavenging of H2O2 by mouse brain mitochondria
#MMPMID25248416
Starkov AA
; Andreyev AY
; Zhang SF
; Starkova NN
; Korneeva M
; Syromyatnikov M
; Popov VN
J Bioenerg Biomembr
2014[Dec]; 46
(6
): 471-7
PMID25248416
show ga
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 H2O2/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 H2O2 added at a concentration of 0.4 ?M, which
is close to the reported physiological H2O2 concentrations in tissues, under
conditions of low and high levels of mitochondrial H2O2 generation. With
NAD-linked substrates, the rate of H2O2 generation by mitochondria was ~50-70
pmol/min/mg. The H2O2 scavenging dynamics was best approximated by the first
order reaction equation. H2O2 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 H2O2 generation was
~2,200-2,900 pmol/min/mg; the scavenging of added H2O2 was masked by a
significant accumulation of generated H2O2 in the assay medium. The obtained data
were fitted into a simple model that reasonably well described the interaction
between H2O2 scavenging and production. It showed that mitochondria are neither a
sink nor a source of H2O2, but can function as both at the same time, efficiently
stabilizing exogenous H2O2 concentration at a level directly proportional to the
ratio of the H2O2 generation rate to the rate constant of the first order
scavenging reaction.
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