Increase of mitochondrial PLA2-released fatty acids is an early event in 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 activated in various TNF-sensitive cell lines. In an attempt to further characterize the mechanism of trans-membrane signalling at the mitochondrial level, we have oriented our investigation to the study of phospholipase A2 activity localized in this organelle isolated from TNF-treated WEHI-164 cells. Under physiological conditions, this enzyme has a very low basal activity near the resting state, while under TNF treatment its activity is dramatically increased. This event is induced by TNF concentrations which also cause cytolysis; however, the activity of this enzyme is increased several hours before maximum cytotoxicity occurs. The activation of the mitochondrial phospholipase A2 is not arachidonoyl or fatty acid selective, as is the case for the cytosolic species. Phospholipase A2 and succinate-dehydrogenase display higher activities simultaneously under TNF treatment. This change in activity is linked to morphologic modifications. Mitochondria in particular display an orthodox state characterized by a large and clear matrix space and few crests.