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- Title
Characteristics of α-glycerophosphate-evoked H<sub>2</sub>O<sub>2</sub> generation in brain mitochondria.
- Authors
Tretter, Laszlo; Takacs, Katalin; Hegedus, Vera; Adam-Vizi, Vera
- Abstract
Characteristics of reactive oxygen species (ROS) production in isolated guinea-pig brain mitochondria respiring on α-glycerophosphate (α-GP) were investigated and compared with those supported by succinate. Mitochondria established a membrane potential (ΔΨm) and released H2O2 in parallel with an increase in NAD(P)H fluorescence in the presence of α-GP (5–40 mm). H2O2 formation and the increase in NAD(P)H level were inhibited by rotenone, ADP or FCCP, respectively, being consistent with a reverse electron transfer (RET). The residual H2O2 formation in the presence of FCCP was stimulated by myxothiazol in mitochondria supported by α-GP, but not by succinate. ROS under these conditions are most likely to be derived from α-GP-dehydrogenase. In addition, huge ROS formation could be provoked by antimycin in α-GP-supported mitochondria, which was prevented by myxothiazol, pointing to the generation of ROS at the quinol-oxidizing center (Qo) site of complex III. FCCP further stimulated the production of ROS to the highest rate that we observed in this study. We suggest that the metabolism of α-GP leads to ROS generation primarily by complex I in RET, and in addition a significant ROS formation could be ascribed to α-GP-dehydrogenase in mammalian brain mitochondria. ROS generation by α-GP at complex III is evident only when this complex is inhibited by antimycin.
- Subjects
MITOCHONDRIA; OXIDATIVE stress; REACTIVE oxygen species; NEURONS; SUCCINATE dehydrogenase; DEHYDROGENASES; CHARGE exchange
- Publication
Journal of Neurochemistry, 2007, Vol 100, Issue 3, p650
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2006.04223.x