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- Title
Ca<sup>2+</sup>-induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex I.
- Authors
Votyakova, Tatyana V.; Reynolds, Ian J.
- Abstract
Mitochondrial complex I dysfunction has been implicated in a number of brain pathologies, putatively owing to an increased rate of reactive oxygen species (ROS) release. However, the mechanisms regulating the ROS burden are poorly understood. In this study we investigated the effect of Ca2+ loads on ROS release from rat brain mitochondria with complex I partially inhibited by rotenone. The addition of 20 nmrotenone to brain mitochondria increased ROS release. Ca2+ (100 µm) alone had no effect on ROS release, but greatly potentiated the effects of rotenone. The effect of Ca2+ was decreased by ruthenium red. Ca2+-challenged mitochondria lose about 88% of their glutathione and 46% of their cytochromecunder these conditions, although this depends only on Ca2+ loading and not complex I inhibition. ADP in combination with oligomycin decreased the loss of glutathione and cytochromecand free radical generation. Cyclosporin A alone was ineffective in preventing these effects, but augmented the protection provided by ADP and oligomycin. Non-specific permeabilization of mitochondria with alamethicin also increased the ROS signal, but only when combined with partial inhibition of complex I. These results demonstrate that Ca2+ can greatly increase ROS release by brain mitochondria when complex I is impaired.
- Subjects
MITOCHONDRIA; BRAIN; MITOCHONDRIAL pathology; CELLULAR pathology; BOTANICAL insecticides; GLUTATHIONE; PREVENTIVE medicine; DISEASES; REACTIVE oxygen species; CYCLOSPORINE
- Publication
Journal of Neurochemistry, 2005, Vol 93, Issue 3, p526
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2005.03042.x