INCREASE OF MITOCHONDRIAL PLA2-RELEASED FATTY-ACIDS IS AN EARLY EVENTIN TUMOR-NECROSIS-FACTOR ALPHA-TREATED WEHI-164 CELLS

We have previously reported that TNF induced changes in mitochondrial enzymes, one of which, succinate-dehydrogenase, is specifically activa ted in various TNF-sensitive cell lines. In an attempt to further char acterize the mechanism of trans-membrane signalling at tile mitochondr ial level, we have oriented our investigation to the study of phosphol ipase A2 activity localized in this organelle isolated from TNF-treate d WEHI-164 cells. Under physiological conditions, this enzyme has a ve ry low basal activity near the resting state, while under TNF treatmen t its activity is dramatically increased. This event is induced by TNF concentrations which also cause cytolysis; however, the activity of t his enzyme is increased several hours before maximum cytotoxicity occu rs. The activation of the mitochondrial phospholipase A2 is not arachi donoyl or fatty acid selective, as is the case for the cytosolic speci es. Phospholipase A2 and succinate-drhydrogenase display higher activi ties simultaneously under TNF treatment. This change in activity is li nked to morphologic modifications. Mitochondria in particular display an orthodox state characterized by a large and clear matrix space and few crests. (C) 1996 Academic Press, Inc.