1. A study of the mode and mechanism of Cu2+-induced mitochondrial swelling was carried out. 2. Mitochondrial swelling curves (E520 turbidity changes) were obtained as a function of [Cu2+], pH, temperature and mitochondrial protein concentration. ED50 was approx. 70mμmoles of Cu2+. Calculation of the activation energy from the Arrhenius equation gave a value of 22900cal./mole per degree with Q10 4·02. 3. No lipid peroxides were formed during swelling. 4. Changes in oxygen consumption (Clark-type electrode) were dependent on the substrate used, but revealed no increased uptake in presence of Cu2+. 5. Cu2+-induced swelling was inhibited by EDTA, 8-hydroxyquinoline, cyanide, citrate, bovine serum albumin, ATP, glutamate, GSH, dithiothreitol and sucrose. Azide, Amytal, antimycin A and oligomycin had no significant effect. Potentiation of swelling was seen with ascorbate, 2,4-dinitrophenol and succinate. 6. The occurrence of different types of mitochondrial swelling and the suggestion that Cu2+-induced swelling is mediated through a stoicheiometric interaction with a thiol-containing membrane receptor are discussed.

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