Dissociation Of Nad(p)+-stimulated Mitochondrial Ca2+ Efflux From Swelling And Membrane Damage

NAD(P)+-stimulated Ca2+ efflux from mitochondria in a high-sucrose medium is irreversible and is accompanied by large-amplitude mitochondrial swelling and membrane damage. If sucrose is partially replaced by polyethylene glycol (Mr ≅ 1000) as osmolar supporting medium, Ca2+ efflux is still stimulated by NAD(P)+ but mitochondrial swelling is eliminated. Other experiments in a high-sucrose medium showed that the lag phase between NAD(P)H oxidation and the beginning of net Ca2+ efflux decreases with increasing temperature. At 37 °C Ca2+ efflux precedes mitochondrial swelling, even in a high-sucrose medium, showing that the mitochondrial damage, as reflected by large-amplitude swelling, is not obligatory for Ca2+ efflux induced by the oxidized state of mitochondrial NAD(P)+. If a high-sucrose medium is supplemented with 20 mm potassium acetate, longer periods of Ca2+ release can be observed before the appearance of swelling. Under these experimental conditions the release of Ca2+ can be completely reversed if the rereduction of NAD(P)+ is brought about by the addition of the reductants β-hydroxybutyrate and isocitrate. © 1984.23218691Lehninger, (1970) Biochem. J, 119, pp. 129-138Saris, Åkerman, (1980) Curr. Topics Bioenerg, 10, pp. 104-179Fiskum, Lehninger, (1981) Calcium and Cell Function, 2, pp. 39-80. , W.Y. Cheung, Academic Press, New YorkNicholls, Åkerman, (1982) Biochim. Biophys. Acta, 683, pp. 57-88Hansford, Castro, (1982) J. Bioenerg. Biomemb, 14, pp. 361-376Joseph, Coll, Cooper, Marks, Williamson, (1983) J. Biol. Chem, 258, pp. 731-741Vercesi, Reynafarje, Lehninger, (1978) J. Biol. Chem, 253, pp. 6379-6385Landry, Lehninger, (1976) Biochem. J, 158, pp. 427-438Lehninger, Vercesi, Bababunmi, (1978) Proc. Natl. Acad. Sci. USA, 75, pp. 1690-1694Coelho, Vercesi, (1980) Arch. Biochem. Biophys, 204, pp. 141-147Fiskum, Lehninger, (1979) J. Biol. Chem, 254, pp. 6236-6239Dawson, Selwyn, Fulton, Inhibition of Ca2+ efflux from mitochondria by nupercaine and tetracaine (1959) Nature, 277, pp. 484-486Arshad, Holdsworth, (1980) J. Memb. Biol, 57, pp. 207-212Lötscher, Winterhalter, Carafoli, Richter, Hydroperoxides can modulate the redox state of pyridine nucleotides and the calcium balance in rat liver mitochondria (1979) Proceedings of the National Academy of Sciences, 76, pp. 4340-4344Nicholls, Brand, (1980) Biochem. J, 188, pp. 113-118Prpic, Bygrave, (1980) J. Biol. Chem, 255, pp. 6193-6199Beatrice, Palmer, Pfeiffer, (1980) J. Biol. Chem, 255, pp. 8663-8671Roth, Dikstein, Inhibition of ruthenium red-insensitive mitochondrial Ca2+ release and its pyridine nucleotide specificity (1981) Biochemical and Biophysical Research Communications, 105, pp. 991-996Palmer, Pfeiffer, (1981) J. Biol. Chem, 256, pp. 6742-6750Bardsley, Brand, (1982) Biochem. J, 202, pp. 197-201Baumhuter, Richter, The hydroperoxide-induced release of mitochondrial calcium occurs via a distinct pathway and leaves mitochondria intact (1982) FEBS Letters, 148, pp. 271-275Beatrice, Stiers, Pfeiffer, (1982) J. Biol. Chem, 257, pp. 7161-7171Charlton, Wenner, (1978) Biochem. J, 170, pp. 537-544Krell, Baur, Pfaff, (1979) Eur. J. Biochem, 101, pp. 349-364Bellomo, Jewell, Thor, Orrenius, (1982) Proc. Natl. Acad. Sci. USA, 79, pp. 6842-6846Sies, Graf, Estrela, (1981) Proc. Natl. Acad. Sci. USA, 78, pp. 3358-3362Zoccarato, Rugolo, Siliprandi, Siliprandi, (1981) Eur. J. Biochem, 114, pp. 195-199Hunter, Haworth, Southard, (1976) J. Biol. Chem, 251, pp. 5069-5077Sitaramam, Sarma, (1981) Proc. Natl. Acad. Sci. USA, 78, pp. 3441-3445Lehninger, (1974) Proc. Natl. Acad. Sci. USA, 71, pp. 1520-1524Al-Shatkhaly, Baum, (1979) Biochem. Soc. Trans, 7, pp. 215-216Moore, Jewell, Bellomo, Orrenius, (1983) FEBS Lett, 153, pp. 289-29