Menadione induces a low conductance state of the mitochondrial inner membrane sensitive to bongkrekic acid

Free Radical Biology & Medicine
Antonio ToninelloChristoph Richter

Abstract

When rat liver mitochondria are allowed to cycle Ca(2+) and are incubated in the presence of the pro-oxidant menadione, they undergo swelling, membrane potential (DeltaPsi) collapse, and ion release. These effects, which are inhibited by cyclosporin A (CsA), are fully consistent with the opening of the so-called permeability transition pore. However, when Ca(2+) cycling is abolished by EGTA, the mitochondria remain energized (DeltaPsi collapse and swelling are avoided), but Ca(2+) efflux, promoted by the chelating agent, is stimulated by menadione. This stimulation goes together with the release of Mg(2+), K(+), and adenine nucleotides (AdN) and is inhibited by bongkrekic acid (BKA). The effect of menadione is also characterized by biphasic NAD(P)H oxidation which becomes monophasic in the presence of BKA, CsA, or EGTA and by the oxidation of thiol groups not restrained by the above-mentioned inhibitors. These results suggest that BKA acts indirectly by preserving in the matrix a critical amount of AdN without modifying the monophasic oxidation of pyridine nucleotides by menadione. A critical number of thiol groups also seems to be involved in the phenomenon. Their oxidation most probably causes a conformational change on adeni...Continue Reading

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Citations

Sep 25, 2012·Chemical Research in Toxicology·Katsuhiro OkudaMitsuru Shindo
Jan 28, 2010·Journal of Cell Science·Vian Azzu, Martin D Brand
Aug 13, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·João P MonteiroPaulo J Oliveira
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Sep 21, 2005·The Journal of Biological Chemistry·Sabino VesceDavid G Nicholls
Jul 11, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alexey G KruglovSvetlana A Kruglova
Aug 28, 2021·International Journal of Molecular Sciences·Ekaterina KharechkinaAlexey Kruglov

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