Free fatty acids activate a vigorous Ca2+: 2H(+) antiport activity in yeast mitochondria

The accumulation and retention of Ca2+ by yeast mitochondria (Saccharomyces cerevisiae) mediated by ionophore ETH 129 occurs with a variable efficienc y in different preparations. Ineffective Ca2+ transport and a depressed mem brane potential occur in parallel, are exacerbated in parallel by exogenous free fatty acids, and are corrected in parallel by the addition of bovine serum albumin. Bovine serum albumin is not required to develop a high membr ane potential when either Ca2+ or ETH 129 are absent, and when both are pre sent membrane potential is restored by the addition of EGTA in a concentrat ion-dependant manner. Respiration and swelling data indicate that the perme ability transition pore does not open in yeast mitochondria that are treate d with Ca2+ and ETH 129, whereas fatty acid concentration studies and the i naction of carboxyatractyloside indicate that fatty acid-derived uncoupling does not underlie the other observations. It is concluded that yeast mitoc hondria contain a previously unrecognized Ca2+:2H(+) antiporter that is hig hly active in the presence of free fatty acids and leads to a futile cycle of Ca2+ accumulation and release when exogenous Ca2+ and ETH 129 are availa ble. It is also shown that isolated yeast mitochondria degrade their phosph olipids at a relatively rapid rate. The activity responsible is also previo usly unrecognized. It is Ca2+-independent, little affected by the presence or absence of a respiratory substrate, and leads to the hydrolysis of ester linkages at both the sn-1 and sn-2 positions of the glycerophospholipids. The products of this activity, through their actions on the antiporter, exp lain the variable behavior of yeast mitochondria treated with Ca2+ plus ETH 129.