Ebselen induces mitochondrial permeability transition because of its interaction with adenine nucleotide translocase

Life Sciences
Natalia PavónEdmundo Chávez

Abstract

Mitochondrial permeability transition is a process established through massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an antioxidant seleno compound, has been introduced as a reagent which inhibits mitochondrial dysfunction induced by permeability transition. Paradoxically enough, it has been shown that Ebs may also be able to induce the opening of the mitochondrial non-selective pores. This study was performed with the purpose of establishing the membrane system involved in Ebs-induced pore opening. Permeability transition was appraised by analyzing the following: i) matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c, and iii) the inhibition of superoxide dismutase. All of these adverse reactions were inhibited by N-ethylmaleimide and cyclosporin A. At concentrations from 5 to 20 μM, we found that Ebs induces non-specific membrane permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin-5-maleimide to the thiol groups of the adenine nucleotide translocase. Based on the above, it is tempting to hypothesize that Ebs induces pore opening through its binding to the ADP/ATP carrier.

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Citations

Feb 24, 2016·Biochimica Et Biophysica Acta·Lucia BiasuttoMario Zoratti
Nov 16, 2018·British Journal of Pharmacology·Luigi LeanzaIldiko Szabo
Aug 31, 2018·Cell Biochemistry and Biophysics·Francisco CorreaEdmundo Chávez
Jul 2, 2021·Nature Reviews. Drug Discovery·Henry Jay Forman, Hongqiao Zhang

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