Induction of the non-selective mitochondrial pore in lymphoid cells. 2. Intact rat thymocytes

Increase of Ca2+ concentration in the cytosol of thymocytes to 400-600 nM c auses slow accumulation of Ca2+ in mitochondria. Release of Ca2+ from mitoc hondria 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 mitoc hondrial membrane. In the presence of oxidizing agents (tert-butyl hydroper oxide and diamide), sub-optimal concentrations of uncoupler induce rapid cy closporin-sensitive release of Ca2+. 6-Ketocholestanol, a recoupler under t hese conditions, causes redistribution of Ca2+ from the cytosol into mitoch ondria. These data indicate that partial uncoupling under conditions of oxi dative stress causes opening of the permeability transition pore in a fract ion of the mitochondria in intact lymphocytes. This mechanism mediates rapi d release of Ca2+ from mitochondria into the cytosol.