DAMAGE TO CA2-LOADED MITOCHONDRIA BY FATTY-ACIDS AND PROTECTIVE EFFECT OF L-CARNITINE()

The effect of palmitate and L-carnitine on Ca2+ capacity of rat liver mitochondria has been studied Ca2+ capacity was estimated as a sum of consecutive Ca2+ additions which result in transient stimulation of re spiration coupled with Ca2+ influx into mitochondria. L-Carnitine incr eases Ca2+ capacity of mitochondria in the presence of ATP. Ca2+ capac ity was increased after 50 mu M ATP or ADP has been added. In all case s carboxyatractylate prevented the increase in Ca2+ capacity. Palmitat e and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) added at concentrations inducing the similar stimulating effect on respirat ion decrease Ca2+ capacity ta about the same extent. The effect of pal mitate is diminished by L-carnitine, the manifestation of the L-carnit ine effect requiring ATP. The data suggest that a protonophoric effect of fatty acids plays a crucial role in Ca2+-dependent damage to mitoc hondria.