Membrane potential and delta pH dependency of reverse electron transport-associated hydrogen peroxide production in brain and heart mitochondria

Succinate-driven reverse electron transport (RET) is one of the main sources of mitochondrial reactive oxygen species (mtROS) in ischemia-reperfusion injury. RET is dependent on mitochondrial membrane potential (Δψ m ) and transmembrane pH difference (ΔpH), components of the proton motive force ( pm...

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Bibliographic Details
Published in:Journal of bioenergetics and biomembranes 2018-10, Vol.50 (5), p.355-365
Main Authors: Komlódi, Tímea, Geibl, Fanni F., Sassani, Matilde, Ambrus, Attila, Tretter, László
Format: Article
Language:English
Subjects:
Animal Anatomy
Animal Biochemistry
Biochemistry
Bioorganic Chemistry
Brain
Chemistry
Chemistry and Materials Science
Dependence
Electron transport
Fluorescence
Glycerophosphate
Guinea pigs
Histology
Hydrogen peroxide
Ionophores
Ischemia
Membrane potential
Mitochondria
Morphology
Nigericin
Organic Chemistry
pH effects
Potassium
Protonmotive force
Reactive oxygen species
Reperfusion
Valinomycin
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Summary:Succinate-driven reverse electron transport (RET) is one of the main sources of mitochondrial reactive oxygen species (mtROS) in ischemia-reperfusion injury. RET is dependent on mitochondrial membrane potential (Δψ m ) and transmembrane pH difference (ΔpH), components of the proton motive force ( pmf ); a decrease in Δψ m and/or ΔpH inhibits RET. In this study we aimed to determine which component of the pmf displays the more dominant effect on RET-provoked ROS generation in isolated guinea pig brain and heart mitochondria respiring on succinate or α-glycerophosphate (α-GP). Δψ m was detected via safranin fluorescence and a TPP + electrode, the rate of H 2 O 2 formation was measured by Amplex UltraRed, the intramitochondrial pH (pH in ) was assessed via BCECF fluorescence. Ionophores were used to dissect the effects of the two components of pmf . The K + /H + exchanger, nigericin lowered pH in and ΔpH, followed by a compensatory increase in Δψ m that led to an augmented H 2 O 2 production. Valinomycin, a K + ionophore, at low [K + ] increased ΔpH and pH in , decreased Δψ m , which resulted in a decline in H 2 O 2 formation. It was concluded that Δψ m is dominant over ∆pH in modulating the succinate- and α-GP-evoked RET. The elevation of extramitochondrial pH was accompanied by an enhanced H 2 O 2 release and a decreased ∆pH. This phenomenon reveals that from the pH component not ∆pH, but rather absolute value of pH has higher impact on the rate of mtROS formation. Minor decrease of Δψ m might be applied as a therapeutic strategy to attenuate RET-driven ROS generation in ischemia-reperfusion injury.
ISSN:0145-479X
1573-6881
DOI:10.1007/s10863-018-9766-8