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Characteristics of α‐glycerophosphate‐evoked H 2 O 2 generation in brain mitochondria
Author(s) -
Tretter Laszlo,
Takacs Katalin,
Hegedus Vera,
AdamVizi Vera
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04223.x
Subject(s) - mitochondrion , antimycin a , nad+ kinase , reactive oxygen species , rotenone , succinate dehydrogenase , mitochondrial ros , biochemistry , chemistry , biology , enzyme
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 (ΔΨ m ) and released H 2 O 2 in parallel with an increase in NAD(P)H fluorescence in the presence of α‐GP (5–40 m m ). H 2 O 2 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 H 2 O 2 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 (Q o ) 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.