CYTOCHROME-C RELEASE FROM BRAIN MITOCHONDRIA IS INDEPENDENT OF THE MITOCHONDRIAL PERMEABILITY TRANSITION

Ca2+ uptake by brain mitochondria induces the release of up to 40% of total cytochrome c in a cyclosporin A-insensitive manner. In the prese nce of ATP and Mg2+, this process is not accompanied by mitochondrial swelling. There is a moderate decrease in membrane potential under the se conditions, but it is completely reversible upon removal of accumul ated Ca2+ by addition of EGTA+A23187 but not by EGTA alone. These obse rvations provide evidence that cytochrome c release from brain mitocho ndria does not require the membrane permeability transition. However, brain mitochondria can undergo the permeability transition in the abse nce of ATP and Mg2+, which results in cyclosporin A-sensitive large am plitude swelling, loss of Ca2+ uptake capacity and release of matrix s olutes. (C) 1998 Federation of European Biochemical Societies.