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Ascorbate and Low Concentrations of FeSO4 Induce the Ca2+-Dependent Pore in Rat Liver Mitochondria

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Abstract

Oxidative stress is one of the most frequent causes of tissue and cell injury in various pathologies. The molecular mechanism of mitochondrial damage under conditions of oxidative stress induced in vitro with low concentrations of FeSO4 and ascorbate (vitamin C) was studied. FeSO4 (1-4 μM) added to rat liver mitochondria that were incubated in the presence of 2.3 mM ascorbate induced (with a certain delay) a decrease in membrane potential and high-amplitude swelling. It also significantly decreased the ability of mitochondria to accumulate exogenous Ca2+. All the effects of FeSO4 + ascorbate were essentially prevented by cyclosporin A, a specific inhibitor of the mitochondrial Ca2+-dependent pore (also known as the mitochondrial permeability transition). EGTA restored the membrane potential of mitochondria de-energized with FeSO4 + ascorbate. We hypothesize that oxidative stress induced in vitro with FeSO4 and millimolar concentrations of ascorbate damages mitochondria by inducing the cyclosporin A-sensitive Ca2+-dependent pore in the inner mitochondrial membrane.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. M. Toreza 44, St. Petersburg, 194223, Russia

    I. V. Brailovskaya

  2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899, Russia

    A. A. Starkov & E. N. Mokhova

Authors
  1. I. V. Brailovskaya
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  2. A. A. Starkov
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  3. E. N. Mokhova
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Brailovskaya, I.V., Starkov, A.A. & Mokhova, E.N. Ascorbate and Low Concentrations of FeSO4 Induce the Ca2+-Dependent Pore in Rat Liver Mitochondria. Biochemistry (Moscow) 66, 909–912 (2001). https://doi.org/10.1023/A:1011913021380

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  • DOI: https://doi.org/10.1023/A:1011913021380

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