Komlodi 2018 J Bioenerg Biomembr

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Komlódi T, Geibl FF, Sassani M, Ambrus A, Tretter L (2018) Membrane potential and delta pH dependency of reverse electron transport-associated hydrogen peroxide production in brain and heart mitochondria. J Bioenerg Biomembr 10.1007/s10863-018-9766-8.

» PMID: 30116920 Open Access

Komlodi T, Geibl FF, Sassani M, Ambrus A, Tretter L (2018) J Bioenerg Biomembr

Abstract: 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 (Δψm) and transmembrane pH difference (ΔpH), components of the proton motive force (pmf); a decrease in Δψm 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). Δψm was detected via safranin fluorescence and a TPP+ electrode, the rate of H2O2 formation was measured by Amplex UltraRed, the intramitochondrial pH (pHin) was assessed via BCECF fluorescence. Ionophores were used to dissect the effects of the two components of pmf. The K+/H+ exchanger, nigericin lowered pHin and ΔpH, followed by a compensatory increase in Δψm that led to an augmented H2O2 production. Valinomycin, a K+ ionophore, at low [K+] increased ΔpH and pHin, decreased Δψm, which resulted in a decline in H2O2 formation. It was concluded that Δψm is dominant over ∆pH in modulating the succinate- and α-GP-evoked RET. The elevation of extramitochondrial pH was accompanied by an enhanced H2O2 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 Δψm might be applied as a therapeutic strategy to attenuate RET-driven ROS generation in ischemia-reperfusion injury.

Keywords: Alpha-glycerophosphate, Membrane potential, Mitochondria, Nigericin, Proton motive force, Reactive oxygen species, Reverse electron transport, Succinate, Valinomycin Bioblast editor: Komlodi T O2k-Network Lab: HU Budapest Tretter L


Labels: MiParea: Respiration, mt-Membrane 

Stress:Oxidative stress;RONS  Organism: Guinea pig  Tissue;cell: Heart, Nervous system  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase  Regulation: mt-Membrane potential, pH  Coupling state: LEAK  Pathway: S, Gp  HRR: Oxygraph-2k, O2k-Protocol, O2k-FluoRespirometer 

Succinate pathway control state, SUIT-009 AmR mt D021