Impairment of pH gradient and membrane potential mediates redox dysfunction in the mitochondria of the post-ischemic heart

Basic Research in Cardiology
Patrick T KangYeong-Renn Chen

Abstract

The mitochondrial electrochemical gradient (Δp), which comprises the pH gradient (ΔpH) and the membrane potential (ΔΨ), is crucial in controlling energy transduction. During myocardial ischemia and reperfusion (IR), mitochondrial dysfunction mediates superoxide (·O2-) and H2O2 overproduction leading to oxidative injury. However, the role of ΔpH and ΔΨ in post-ischemic injury is not fully established. Here we studied mitochondria from the risk region of rat hearts subjected to 30 min of coronary ligation and 24 h of reperfusion in vivo. In the presence of glutamate, malate and ADP, normal mitochondria (mitochondria of non-ischemic region, NR) exhibited a heightened state 3 oxygen consumption rate (OCR) and reduced ·O2- and H2O2 production when compared to state 2 conditions. Oligomycin (increases ΔpH by inhibiting ATP synthase) increased ·O2- and H2O2 production in normal mitochondria, but not significantly in the mitochondria of the risk region (IR mitochondria or post-ischemic mitochondria), indicating that normal mitochondrial ·O2- and H2O2 generation is dependent on ΔpH and that IR impaired the ΔpH of normal mitochondria. Conversely, nigericin (dissipates ΔpH) dramatically reduced ·O2- and H2O2 generation by normal mitochond...Continue Reading

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Citations

Nov 13, 2018·Journal of Cellular Physiology·Farzaneh G TahrirKamel Khalili
Nov 30, 2018·Journal of Cellular Physiology·Yitian ZhengXianhe Lin
Nov 11, 2021·American Journal of Physiology. Cell Physiology·Chwen-Lih ChenYeong-Renn Chen

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