Mitochondrial respiratory chain inhibitors modulate the metal-induced inner mitochondrial membrane permeabilization

• Authors: Elena A Belyaeva
• Languages of publication: EN

Abstracts

EN

To elucidate the molecular mechanisms of the protective action of stigmatellin (an inhibitor of complex III of mitochondrial electron transport chain, mtETC) against the heavy metal-induced cytotoxicity, we tested its effectiveness against mitochondrial membrane permeabilization produced by heavy metal ions Cd2+, Hg2+, Cu2+ and Zn2+, as well as by Ca2+ (in the presence of Pi) or Se (in form of Na2SeO3) using isolated rat liver mitochondria. It was shown that stigmatellin modulated mitochondrial swelling produced by these metals/metalloids in the isotonic sucrose medium in the presence of ascorbate plus tetramethyl-p-phenylenediamine (complex IV substrates added for energization of the mitochondria). It was found that stigmatellin and other mtETC inhibitors enhanced the mitochondrial swelling induced by selenite. However, in the same medium, all the mtETC inhibitors tested as well as cyclosporin A and bongkrekic acid did not significantly affect Cu2+-induced swelling. In contrast, the high-amplitude swelling produced by Cd2+, Hg2+, Zn2+, or Ca2+ plus Pi was significantly depressed by these inhibitors. Significant differences in the action of these metals/metalloids on the redox status of pyridine nucleotides, transmembrane potential and mitochondrial respiration were also observed. In the light of these results as well as the data from the recent literature, our hypothesis on a possible involvement of the respiratory supercomplex, formed by complex I (P-site) and complex III (S-site) in the mitochondrial permeabilization mediated by the mitochondrial transition pore, is updated.

Keywords

EN

copper; mercury; stigmatellin; selenite; permeability transition pore; cadmium; mitochondria; zinc

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2010
• Volume: 57
• Issue: 4
• Pages: 435-441

Dates

published

2010

received

2010-09-01

revised

2010-10-16

accepted

2010-11-12

(unknown)

2010-11-19

Contributors

author

Elena A Belyaeva

• Laboratory of Comparative Biochemistry of Inorganic Ions, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St.-Petersburg, Russia

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