Votyakova 2001 J Neurochem
| Votyakova TV, Reynolds IJ (2001) DeltaPsi(m)-Dependent and -independent production of reactive oxygen species by rat brain mitochondria. J Neurochem 79:266-77. |
Votyakova TV, Reynolds IJ (2001) J Neurochem
Abstract: Mitochondria are widely believed to be the source of reactive oxygen species (ROS) in a number of neurodegenerative disease states. However, conditions associated with neuronal injury are accompanied by other alterations in mitochondrial physiology, including profound changes in the mitochondrial membrane potential ฮฮจm. In this study, we have investigated the effects of ฮฮจm on ROS production by rat brain mitochondria using the fluorescent peroxidase substrates scopoletin and Amplex red. The highest rates of mitochondrial ROS generation were observed while mitochondria were respiring on the complexโII substrate succinate. Under this condition, the majority of the ROS signal was derived from reverse electron transport to complexโI, because it was inhibited by rotenone. This mode of ROS generation is very sensitive to depolarization of ฮฮจm, and even the depolarization associated with ATP generation was sufficient to inhibit ROS production. Mitochondria respiring on the complexโI substrates, glutamate and malate, produce very little ROS until complexโI is inhibited with rotenone, which is also consistent with complexโI being the major site of ROS generation. This mode of oxidant production is insensitive to changes in ฮฮจm. With both substrates, ubiquinone-derived ROS can be detected, but they represent a more minor component of the overall oxidant signal. These studies demonstrate that rat brain mitochondria can be effective producers of ROS. However, the optimal conditions for ROS generation require either a hyperpolarized membrane potential or a substantial level of complexโI inhibition.
Cited by
- Komlodi et al (2022) Hydrogen peroxide production, mitochondrial membrane potential and the coenzyme Q redox state measured at tissue normoxia and experimental hyperoxia in heart mitochondria. MitoFit Preprints 2021 (in prep)
- Komlรณdi et al (2022) The protonmotive force - not merely membrane potential. MitoFit Preprints 2022 (in prep)
- Komlodi et al (2022) Hydrogen peroxide production, mitochondrial membrane potential and the coenzyme Q redox state measured at tissue normoxia and experimental hyperoxia in heart mitochondria. MitoFit Preprints 2021 (in prep)
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MitoFit 2021 Tissue normoxia, MitoFit 2022 pmF
