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Cyclosporin A-Sensitive Cytochrome c Release and Activation of External Pathway of NADH Oxidation in Liver Mitochondria Due to Pore Opening by Acidification of Phosphate-Containing Incubation Medium

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Bioscience Reports

Abstract

Acidification of a high phosphate incubation medium from pH 7.4 to 6.5 promotes increase in rates of succinate oxidation and exogenous NADH oxidation via external (rotenone- and myxothiazol-resistant) pathway by factors 2 and 2.3 respectively. Cyclosporin A prevents these effects. To measure the cytochrome c release, mitochondrial cytochrome c concentration was calculated from absorption spectrum of α-band of cytochromes c+c1. The cytochrome c release is shown to be equal to 27±4%, 40±12%, 70±5% at pH 7.4, 7.0, 6.5, respectively, the last value being reduced by cyclosporin A to 10±3%. Immunoblot method gives the similar results. It is concluded that acidification of the high phosphate medium induces release of a large part of the cytochrome c pool from liver mitochondria due to opening the Ca2+-dependent cyclosporin A-sensitive permeability transition pore and subsequent high amplitude swelling.

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Authors
  1. D.A. Knorre
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  2. V.I. Dedukhova
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  3. M. Yu. Vyssokikh
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  4. E.N. Mokhova
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Knorre, D., Dedukhova, V., Vyssokikh, M.Y. et al. Cyclosporin A-Sensitive Cytochrome c Release and Activation of External Pathway of NADH Oxidation in Liver Mitochondria Due to Pore Opening by Acidification of Phosphate-Containing Incubation Medium. Biosci Rep 23, 67–75 (2003). https://doi.org/10.1023/A:1025520222933

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