CYCLOSPORINE A-SENSITIVE RELEASE OF CA2+ FROM MITOCHONDRIA IN INTACT THYMOCYTES

Release of Ca2+ from mitochondria into cytosol in intact thymocytes wa s studied using the fluorescent dye Fluo-3. It was shown that the rele ase of Ca2+ induced by the dithiol crosslinking agent phenylarsine oxi de or by uncoupler was strongly inhibited by cyclosporin A, a specific inhibitor of the permeability transition pore (PTP) in mitochondria. Oxidative stress sensitized the pore so even partial uncoupling caused rapid cyclosporin A-sensitive release of Ca2+. The experiments on dig itonin-permeabilized cells confirmed that uncoupling induced opening o f the PTP, which forms the major pathway for rapid release of Ca2+ fro m thymocyte mitochondria. (C) 1997 Federation of European Biochemical Societies.