Free Fatty Acids Activate a Vigorous Ca2+:2H+ Antiport Activity in Yeast Mitochondria
Bradshaw PC, Jung DW, Pfeiffer DR
Journal of Biological Chemistry (2001)
Category: calcium, mitochondria-transport ¤ Added: Feb 20, 2006 ¤ Rating: ◊◊
The accumulation and retention of Ca2 by yeast mitochondria (Saccharomyces cerevisiae) mediated by ionophore ETH 129 occurs with a variable efficiency in different preparations. Ineffective Ca2 transport and a depressed membrane 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 membrane potential when either Ca2 or ETH 129 are absent, and when both are present membrane potential is restored by the addition of EGTA in a concentration-dependant manner. Respiration and swelling data indicate that the permeability transition pore does not open in yeast mitochondria that are treated with Ca2 and ETH 129, whereas fatty acid concentration studies and the inaction of carboxyatractyloside indicate that fatty acid-derived uncoupling does not underlie the other observations. It is concluded that yeast mitochondria contain a previously unrecognized Ca2:2H antiporter that is highly 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 available. It is also shown that isolated yeast mitochondria degrade their phospholipids at a relatively rapid rate. The activity responsible is also previously 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, explain the variable behavior of yeast mitochondria treated with Ca2 plus ETH 129.