Induction of the Non-selective Mitochondrial Pore in Lymphoid Cells. 2. Intact Rat Thymocytes

B. V. Chernyak

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-3181; E-mail: chernyak@pcman.genebee.msu.su

Received December 8, 1998; Revision received March 1, 1999

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Increase of Ca²⁺ concentration in the cytosol of thymocytes to 400-600 nM causes slow accumulation of Ca²⁺ in mitochondria. Release of Ca²⁺ from mitochondria into the cytosol is induced by an uncoupler (FCCP) or by a dithiol cross-linking agent (phenylarsine oxide) and is inhibited by cyclosporin A--a specific inhibitor of the permeability transition pore in the inner mitochondrial membrane. In the presence of oxidizing agents (tert-butyl hydroperoxide and diamide), sub-optimal concentrations of uncoupler induce rapid cyclosporin-sensitive release of Ca²⁺. 6-Ketocholestanol, a recoupler under these conditions, causes redistribution of Ca²⁺ from the cytosol into mitochondria. These data indicate that partial uncoupling under conditions of oxidative stress causes opening of the permeability transition pore in a fraction of the mitochondria in intact lymphocytes. This mechanism mediates rapid release of Ca²⁺ from mitochondria into the cytosol.

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KEY WORDS: thymocytes, mitochondria, cyclosporin-sensitive pore, oxidative stress, uncoupling

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